bims-bac4me 2024-12-08 papers

bims-bac4me

Biomed News

on Microbiome and trained immunity

Issue of 2024–12–08
28 papers selected by
Chun-Chi Chang, Universitäts Spital Zürich

Staphylococcus aureus induced trained immunity in macrophages confers heterologous protection against gram-negative bacterial infection.
Human airway macrophages are metabolically reprogrammed by IFN-γ resulting in glycolysis-dependent functional plasticity.
Macrophages and the microbiome in chronic obstructive pulmonary disease.
Comparison of the bacterial microbiome in the pharynx and nasal cavity of persistent, intermittent carriers and non-carriers of Staphylococcus aureus.
Exopolysaccharides from Bifidobacterium longum subsp. infantis and Bifidobacterium adolescentis modulate Toll-like receptor signaling.
Allergen-Specific Immunotherapy and Trained Immunity.
Understanding the role of Staphylococcus aureus in atopic dermatitis: strain diversity, microevolution, and prophage influences.
Targeted Initiation of Trained Immunity in Tumor-Associated Macrophages with Membrane-Camouflaged Bacillus Calmette-Guérin for Lung Carcinoma Immunotherapy.
Innate Immune Cell Functions Contribute to Spontaneous HIV Control.
Development of immunocompetent full thickness skin tissue constructs to model skin fibrosis for high-throughput drug screening.
Dissecting metabolic landscape of alveolar macrophage.
Fat cells have long-lasting (epigenetic) memory.
The role of the interplay between macrophage glycolytic reprogramming and NLRP3 inflammasome activation in acute lung injury/acute respiratory distress syndrome.
Microbiota transplantation.
Small cyclic dipeptide produced by Lactobacillus rhamnosus with anti-biofilm properties against Streptococcus mutans biofilm.
The Skin Microbiome in the First Year of Life and Its Association With Atopic Dermatitis.
Macrophage polarization in sepsis: Emerging role and clinical application prospect.
Infection of Helicobacter pylori contributes to the progression of gastric cancer through ferroptosis.
Hyaluronan provokes inflammation but suppresses phagocytotic function in macrophages.
Advances in Microbiome-Based Therapeutics for Dermatological Disorders: Current Insights and Future Directions.
Imperfect wound healing sets the stage for chronic diseases.
Programmed cell death: molecular mechanisms, biological functions, diseases, and therapeutic targets.
How to ensure only dying cells rupture.
Prevalence and molecular epidemiology of methicillin-resistant Staphylococcus aureus in livestock farmers, livestock, and livestock products in southern Sri Lanka: A one health approach.
Nasal Mucus Cytokines Are Correlated with Spirometry Measures in CRS Patients with Comorbid Asthma.
Ferroptosis in Osteoarthritis: Towards Novel Therapeutic Strategy.
Guardians of immune privilege.
Comparison of nasal microbiota between preterm and full-term infants in early life.

iScience. 2024 Dec 20. 27(12): 111284

Staphylococcus aureus induced trained immunity in macrophages confers heterologous protection against gram-negative bacterial infection.

Simon R Carlile, Seán C Cahill, Eóin C O'Brien, Nuno G B Neto, Michael G Monaghan, Rachel M McLoughlin.

  Staphylococcus aureus can induce trained immunity in murine macrophages offering protection against repeat exposure during S. aureus skin infection. Here we demonstrate that S. aureus exposure can result in non-specific trained immunity in humans and mice, enhancing macrophage responsiveness and bacterial clearance in a heterologous challenge. In humans, the enhanced macrophage responsiveness was accompanied by metabolic changes and histone modification. In mice, the enhanced responsiveness of macrophages occurred in conjunction with enhanced myelopoiesis. This report provides further insights on the host's response to the bacterium S. aureus, indicating that exposure to this organism induces heterologous protection against subsequent gram-negative infection that is provided by macrophages. These findings support the hypothesis that S. aureus has evolved to develop a mutualistic relationship with the host, imbuing the host with enhanced capacity to protect itself from attack by alternative pathogens, while potentially allowing S. aureus to exert its dominance within its niche.

Keywords:  Immunology; Microbiology

DOI:  https://doi.org/10.1016/j.isci.2024.111284
Elife. 2024 Dec 02. pii: RP98449. [Epub ahead of print]13

Human airway macrophages are metabolically reprogrammed by IFN-γ resulting in glycolysis-dependent functional plasticity.

Donal J Cox, Sarah A Connolly, Cilian Ó Maoldomhnaigh, Aenea A I Brugman, Olivia Sandby Thomas, Emily Duffin, Karl M Gogan, Oisin Ó Gallchobhair, Dearbhla M Murphy, Sinead A O'Rourke, Finbarr O'Connell, Parthiban Nadarajan, James J Phelan, Laura E Gleeson, Sharee A Basdeo, Joseph Keane.

  Airway macrophages (AM) are the predominant immune cell in the lung and play a crucial role in preventing infection, making them a target for host directed therapy. Macrophage effector functions are associated with cellular metabolism. A knowledge gap remains in understanding metabolic reprogramming and functional plasticity of distinct human macrophage subpopulations, especially in lung resident AM. We examined tissue-resident AM and monocyte-derived macrophages (MDM; as a model of blood derived macrophages) in their resting state and after priming with IFN-γ or IL-4 to model the Th1/Th2 axis in the lung. Human macrophages, regardless of origin, had a strong induction of glycolysis in response to IFN-γ or upon stimulation. IFN-γ significantly enhanced cellular energetics in both AM and MDM by upregulating both glycolysis and oxidative phosphorylation. Upon stimulation, AM do not decrease oxidative phosphorylation unlike MDM which shift to 'Warburg'-like metabolism. IFN-γ priming promoted cytokine secretion in AM. Blocking glycolysis with 2-deoxyglucose significantly reduced IFN-γ driven cytokine production in AM, indicating that IFN-γ induces functional plasticity in human AM, which is mechanistically mediated by glycolysis. Directly comparing responses between macrophages, AM were more responsive to IFN-γ priming and dependent on glycolysis for cytokine secretion than MDM. Interestingly, TNF production was under the control of glycolysis in AM and not in MDM. MDM exhibited glycolysis-dependent upregulation of HLA-DR and CD40, whereas IFN-γ upregulated HLA-DR and CD40 on AM independently of glycolysis. These data indicate that human AM are functionally plastic and respond to IFN-γ in a manner distinct from MDM. These data provide evidence that human AM are a tractable target for inhalable immunomodulatory therapies for respiratory diseases.

Keywords:  Mycobacterium tuberculosis; airway macrophages; cytokines; human; immunology; inflammation; lipopolysaccharide; metabolism; polarization

DOI:  https://doi.org/10.7554/eLife.98449
Eur Respir Rev. 2024 Oct;pii: 240053. [Epub ahead of print]33(174):

Macrophages and the microbiome in chronic obstructive pulmonary disease.

Karanjot K Sandhu, Aaron Scott, Amanda L Tatler, Kylie B R Belchamber, Michael J Cox.

COPD is a heterogeneous disease of the lungs characterised by restricted airflow. Chronic inflammation and recurrent bacterial infections are known to be important driving factors in exacerbations of this disease. Despite a marked increase in the number of alveolar macrophages present in the lungs of COPD patients, there is evidence of reduced clearance of pathogenic bacteria, leading to recurrent infection, exacerbation and subsequent lung function decline. This is thought to be attributed to a defect in the phagocytic capability of both alveolar and monocyte-derived macrophages in COPD. In addition to this defect, there is apparent selectivity in bacterial uptake by COPD macrophages because certain pathogenic genera, such as Haemophilus, Moraxella and Streptococcus, are taken up more readily than others. The respiratory microbiome plays a key role in regulating the host immune response both in health and during chronic inflammation. In patients with COPD, there are distinct changes in the composition of the respiratory microbiome, particularly the lower respiratory tract, where dominance of clinically relevant pathogenic species is commonly observed. Whether there are links between these changes in the microbiome and dysfunctional macrophage phagocytosis has not yet been widely studied. This review aims to discuss what is currently known about these phenomena and to explore interactions between macrophages and the respiratory microbiome.

DOI: https://doi.org/10.1183/16000617.0053-2024
J Med Microbiol. 2024 Dec;73(12):

Comparison of the bacterial microbiome in the pharynx and nasal cavity of persistent, intermittent carriers and non-carriers of Staphylococcus aureus.

Samuel González-García, Aida Hamdan-Partida, Julia Pérez-Ramos, José Félix Aguirre-Garrido, Anaíd Bustos-Hamdan, Jaime Bustos-Martínez.

  Introduction.Staphylococcus aureus is a bacterium that colonizes various human sites. The pharynx has been considered as a site of little clinical relevance and little studied. Recently, it has been reported that S. aureus can colonize more the pharynx than the nose. In addition, S. aureus can persist in these sites for prolonged periods of time.Hypothesis. The composition of the pharyngeal and nasal microbiome will differ between persistent, intermittent carriers and non-carriers of S. aureus.Aim. Determine whether the pharyngeal and nasal microbiome is different between carriers and non-carriers of S. aureus.Methodology. S. aureus carriers were monitored by means of pharyngeal and nasal exudates of apparently healthy adult university students for 3 months. Samples from individuals of the same carrier type were pooled, and DNA was extracted and the 16S rRNA was sequenced. The sequences were analysed in MOTHUR v.1.48.0 software, by analysing the percentages of relative abundance in the STAMP 2.1.3 program, in addition to the predictive analysis of metabolic pathways in PICRUSt2.Results. A greater colonization of S. aureus was found in the pharynx than in the nose. The microbiomes of S. aureus carriers and non-carriers do not show significant differences. The main microbiome difference found was between pharyngeal and nasal microbiomes. No significant differences were found in the abundance of the genus Staphylococcus in pharyngeal and nasal S. aureus carriers and non-carriers. The nasal microbiome was found to have more variation compared to the pharyngeal microbiome, which appears to be more stable between individuals and pools. Predictive analysis of metabolic pathways showed a greater presence of Staphylococcus-associated pathways in the nose than in the pharynx.Conclusion. S. aureus can colonize and persist in the pharynx in equal or greater proportion than in the nose. No statistically significant differences were found in the microbiome of the pharyngeal and nasal carriers and non-carriers of S. aureus, but the pharyngeal and nasal microbiomes are different independent of the type of S. aureus carrier or non-carrier. Therefore, the microbiome apparently does not influence the persistence of S. aureus.

Keywords:  Staphylococcus aureus; carriers; metagenomic comparison; non-carriers; nose; pharynx

DOI:  https://doi.org/10.1099/jmm.0.001940
Carbohydr Polym. 2025 Feb 01. pii: S0144-8617(24)01243-8. [Epub ahead of print]349(Pt B): 123017

Exopolysaccharides from Bifidobacterium longum subsp. infantis and Bifidobacterium adolescentis modulate Toll-like receptor signaling.

Renate Akkerman, Marjolein M P Oerlemans, Michela Ferrari, Cynthia Fernández-Lainez, Marthe T C Walvoort, Paul de Vos.

   BACKGROUND: Exopolysaccharides (EPS) from probiotic bacteria like bifidobacteria, have gained considerable attention for the beneficial effects they exert in the gastrointestinal environment. Here, we investigated whether EPS isolated from Bifidobacterium longum subsp. infantis and Bifidobacterium adolescentis can interact with Toll-like receptors (TLRs) in a structure-dependent way and subsequently we investigated whether they influence cytokine-production in dendritic cells (DCs).
RESULTS: EPS from both B. infantis and B. adolescentis were found to be structurally different and were able to inhibit signaling of TLR2 and TLR4 in an EPS-type dependent fashion. EPS from B. infantis was shown to have stronger inhibitory effects on TLR2/1, whereas EPS from B. adolescentis showed stronger effects for TLR2/6 and TLR4. Incubation of DCs with EPS alone had no effect, however stimulation of DCs with spend-medium of epithelial cells incubated with EPS reduced production of the cytokines MCP-1/CCL2 and TNFα.
CONCLUSION: Here we show that EPS from B. infantis and B. adolescentis have structure-dependent immunomodulatory effects, indicating that EPS might be important effector molecules responsible for the health benefits of bifidobacteria.

Keywords:  Bifidobacteria; Dendritic cells; Exopolysaccharides; Immunomodulation; Toll-like receptors

DOI:  https://doi.org/10.1016/j.carbpol.2024.123017
Allergy. 2024 Dec 06.

Allergen-Specific Immunotherapy and Trained Immunity.

Leticia Martín-Cruz, Oscar Palomares.

  The high prevalence of allergic diseases reached over the last years is attributed to the complex interplay of genetic factors, lifestyle changes, and environmental exposome. Allergen-specific immunotherapy (AIT) is the single therapeutic strategy for allergic diseases with the potential capacity to modify the course of the disease. Our knowledge of the mechanisms involved in allergy and successful AIT has significantly improved. Recent findings indicate that long-term allergen tolerance upon AIT discontinuation not only relies on the generation of proper adaptive immune responses by the generation of allergen-specific regulatory T and B cells enabling the induction of different isotypes of blocking antibodies but also relies on the restoration of proper innate immune responses. Trained immunity (TRIM) is the process by which innate immune cells acquire memory by mechanisms depending on metabolic and epigenetic reprogramming, thus conferring the host with increased broad protection against infection. This concept was initially explored for infectious diseases, as well as for vaccination against infections, but compelling experimental evidence suggests that TRIM might also play a role in allergy and AIT. Hyperinflammatory innate immune responses in early life, likely due to TRIM maladaptations, lead to aberrant type 2 inflammation-enhancing allergy. However, exposure to farming environments and specific microbes prevents recurrent infections and allergy development, likely due to mechanisms partially depending on TRIM. TRIM-based vaccines and next-generation AIT vaccines inducing metabolic and epigenetic reprogramming in innate immune cells and their precursors have shown protective antiallergic effects. A better understanding of the factors involved in early-life TRIM mechanisms in the context of allergy and the identification and characterization of novel tolerance inducers might well enable the design of alternative TRIM-based allergen vaccines for allergic diseases.

Keywords:  allergen‐specific immunotherapy; asthma; food allergy; metabolic and epigenetic rewiring; trained immunity; trained immunity‐based allergen vaccines; trained immunity‐based vaccines (TIbV)

DOI:  https://doi.org/10.1111/all.16423
Front Med (Lausanne). 2024 ;11 1480257

Understanding the role of Staphylococcus aureus in atopic dermatitis: strain diversity, microevolution, and prophage influences.

Zhongjie Wang, Claudia Hülpüsch, Claudia Traidl-Hoffmann, Matthias Reiger, Michael Schloter.

  Atopic dermatitis (AD) is a prevalent inflammatory skin disorder characterized by chronic inflammation, skin barrier dysfunction, and microbial dysbiosis, with Staphylococcus aureus playing a significant role in its pathogenesis. This paper explores the strain diversity and microevolution of S. aureus within AD patients, emphasizing how specific strains adapt to the altered skin environment, exacerbating the condition. The review emphasizes the significance of variation in specific functional genes among S. aureus strains, which enhances their ability to adapt to different microenvironments and shapes their pathogenic potential. It also discusses how mobile genetic elements, particularly prophages, contribute to genetic diversity and drive the virulence and antibiotic resistance of S. aureus in AD, highlighting the clinical challenges posed by these strain-specific factors in managing the disease. The paper advocates for the integration of advanced genomic tools such as whole-genome sequencing and machine learning to develop targeted therapies. By focusing on the genetic adaptability of S. aureus and its impact on AD, this review underscores the need for strain-specific diagnostics and personalized treatment strategies to improve patient outcomes.

Keywords:  Staphylococcus aureus; antibiotic resistance; atopic dermatitis; horizontal gene tranfer; microevolution; prophage; strain diversity

DOI:  https://doi.org/10.3389/fmed.2024.1480257
ACS Nano. 2024 Dec 04.

Targeted Initiation of Trained Immunity in Tumor-Associated Macrophages with Membrane-Camouflaged Bacillus Calmette-Guérin for Lung Carcinoma Immunotherapy.

Libo Zhang, Ziyuan Xiao, Dexin Zhang, Lixin Yang, Ziyang Yuan, Guodong Wang, Xue Rui, Qiang Fu, Yong Song, Ke Ren, Haishi Qiao.

  Inducing trained immunity in macrophages is an increasingly promising strategy for preventing cancer development. However, it has not been investigated whether trained immunity in tumor-associated macrophages (TAMs) can be initiated for antitumor applications. Here, we provide a practical strategy that utilizes the macrophage membrane (M) to camouflage Bacillus Calmette-Guérin (M@BCG), endowing it with the capability to selectively target tumors and efficiently induce trained immunity for TAMs. Using a mouse model of Lewis lung carcinoma, we show that the introduction of macrophage membrane increases BCG's accumulation in orthotopic lung cancer tissues compared with naked BCG. The superior tumor-targeting ability can augment BCG-mediated trained immunity in TAMs, leading to a robust activation of immune responses. Furthermore, macrophage depletion and adoptive transfer of BCG-trained TAM experiments demonstrate that the antitumor activity of M@BCG is dependent on the trained immunity of TAMs. More importantly, intravenous administration of M@BCG can synergistically reinforce the antitumor activity of immune checkpoint blockade without causing systemic toxicity. Taken together, our study demonstrates the successful initiation of trained immunity in TAMs using M@BCG, which exhibits prominent antitumor performance through immune activation.

Keywords:  Bacillus Calmette-Guérin (BCG); immunotherapy; targeted delivery; trained immunity; tumor-associated macrophages (TAMs)

DOI:  https://doi.org/10.1021/acsnano.4c11658
Curr HIV/AIDS Rep. 2024 Nov 30. 22(1): 6

Innate Immune Cell Functions Contribute to Spontaneous HIV Control.

Alisa Huber, Floor S Baas, Andre J A M van der Ven, Jéssica C Dos Santos.

   PURPOSE OF REVIEW: To review the role of innate immune cells in shaping the viral reservoir and maintenance of long-term viral control of spontaneous Elite and Viremic HIV controllers.
RECENT FINDINGS: HIV controllers exhibit a smaller and transcriptionally suppressed viral reservoir. Different studies report that early responses from innate cells play a pivotal role in this reservoir configuration. NK cells, particularly those with cytotoxic activity and polyfunctional monocytes, have been linked to viral control, and DCs may contribute through early viral sensing and activation of adaptive responses. In some cases, cytotoxic NK cells appeared before HIV-specific CD8 + T cells, underscoring their importance in early viral suppression. Innate immune cells, including NK cells, monocytes, DCs, and γδ T-cells, are crucial in shaping the viral reservoir in HIV controllers. Early, robust innate responses may help to maintain long-term viral suppression and offer insights into potential therapeutic approaches.

Keywords:  HIV elite control; HIV infection; HIV reservoir; Innate immunity; Trained immunity

DOI:  https://doi.org/10.1007/s11904-024-00713-0
Biofabrication. 2024 Dec 02.

Development of immunocompetent full thickness skin tissue constructs to model skin fibrosis for high-throughput drug screening.

Yi Wei Lim, Russell Quinn, Kapil Bharti, Marc Ferrer, Hoda Zarkoob, Min Jae Song.

  The lack of the immune component in most of the engineered skin models remains a challenge to study the interplay between different immune and non-immune cell types of the skin. Immunocompetent human in vitro skin models offer potential advantages in recapitulating in vivo like behavior which can serve to accelerate translational research and therapeutics development for skin diseases. Here we describe a 3D human full-thickness skin (FTS) equivalent incorporating polarized M1 and M2 macrophages from human peripheral CD14+ monocytes. This macrophage-incorporated FTS model demonstrates discernible immune responses with physiologically relevant cytokine production and macrophage plasticity under homeostatic and lipopolysaccharide stimulation conditions. M2-incorporated FTS recapitulates skin fibrosis phenotypes with transforming growth factor-β1 treatment as reflected by significant collagen deposition and myofibroblast expression, demonstrating a M2 potentiation effect. In conclusion, we successfully biofabricated an immunocompetent FTS with functional macrophages in a high-throughput (HT) amenable format. This model is the first step towards a HT-assay platform to develop new therapeutics for skin diseases.&#xD.

Keywords:  fibrosis; high-throughput; immunocompetence; macrophage; skin model

DOI:  https://doi.org/10.1088/1758-5090/ad998c
Sci Rep. 2024 Dec 05. 14(1): 30383

Dissecting metabolic landscape of alveolar macrophage.

Sunayana Malla, Karuna Anna Sajeevan, Bibek Acharya, Ratul Chowdhury, Rajib Saha.

The highly plastic nature of Alveolar Macrophage (AM) plays a crucial role in the defense against inhaled particulates and pathogens in the lungs. Depending on the signal, AM acquires either the classically activated M1 phenotype or the alternatively activated M2 phenotype. In this study, we investigate the metabolic shift in the activated phases of AM (M1 and M2 phases) by reconstructing context specific Genome-Scale Metabolic (GSM) models. Metabolic pathways such as pyruvate metabolism, arachidonic acid metabolism, chondroitin/heparan sulfate biosynthesis, and heparan sulfate degradation are found to be important driving forces in the development of the M1/M2 phenotypes. Additionally, we formulated a bilevel optimization framework named MetaShiftOptimizer to identify minimal modifications that shift one activated state (M1/M2) to the other. The identified reactions involve metabolites such as glycogenin, L-carnitine, 5-hydroperoxy eicosatetraenoic acid, and leukotriene B4, which show potential to be further investigated as significant factors for developing efficient therapy targets for severe respiratory disorders in the future. Overall, our study contributes to the understanding of the metabolic capabilities of the M1 and M2 phenotype of AM and identifies pathways and reactions that can be potential targets for polarization shift and also be used as therapeutic strategies against respiratory diseases.

DOI: https://doi.org/10.1038/s41598-024-81253-w
Nat Rev Mol Cell Biol. 2024 Dec 03.

Fat cells have long-lasting (epigenetic) memory.

Kim Baumann.

DOI: https://doi.org/10.1038/s41580-024-00816-x
Clin Transl Med. 2024 Dec;14(12): e70098

The role of the interplay between macrophage glycolytic reprogramming and NLRP3 inflammasome activation in acute lung injury/acute respiratory distress syndrome.

Lan Luo, Xiaoli Zhuang, Lin Fu, Ziyuan Dong, Shuyuan Yi, Kan Wang, Yu Jiang, Ju Zhao, Xiaofang Yang, Feilong Hei.

  Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a severe respiratory condition associated with elevated morbidity and mortality. Understanding their complex pathophysiological mechanisms is crucial for developing new preventive and therapeutic strategies. Recent studies highlight the significant role of inflammation involved in ALI/ARDS, particularly the hyperactivation of the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome in macrophages. This activation drives pulmonary inflammation by releasing inflammatory signalling molecules and is linked to metabolic reprogramming, marked by increased glycolysis and reduced oxidative phosphorylation. However, the relationship between NLRP3 inflammasome activation and macrophage glycolytic reprogramming in ALI/ARDS, as well as the molecular mechanisms regulating these processes, remain elusive. This review provides a detailed description of the interactions and potential mechanisms linking NLRP3 inflammasome activation with macrophage glycolytic reprogramming, proposing that glycolytic reprogramming may represent a promising therapeutic target for mitigating inflammatory responses in ALI/ARDS. KEY POINTS: NLRP3 inflammasome activation is pivotal in mediating the excessive inflammatory response in ALI/ARDS. Glycolytic reprogramming regulates NLRP3 inflammasome activation. Therapeutic potential of targeting glycolytic reprogramming to inhibit NLRP3 inflammasome activation in ALI/ARDS.

Keywords:  NLRP3 inflammasome; acute lung injury/acute respiratory distress syndrome; glycolytic reprogramming; macrophage

DOI:  https://doi.org/10.1002/ctm2.70098
Heliyon. 2024 Oct 30. 10(20): e39047

Microbiota transplantation.

Javad Nezhadi, Manouchehr Fadaee, Somayeh Ahmadi, Hossein Samadi Kafil.

  Microbiota refers to a collection of living microorganisms, including bacteria, yeasts, and viruses, that coexist in various sites of the human body. Microbiota can perform multiple functions in the body, which have an essential effect on human health and homeostasis. For example, the microbiota can digest polysaccharides, produce vitamins, modulate the immune system, and protect the body against pathogens. Various factors can occasionally alter the microbiota population in the human body, a condition known as dysbiosis. Dysbiosis can disrupt the homeostasis of a person's body and cause disease. Recent years have witnessed efforts to restore the microbiota population of an individual's body to its original state and eradicate dysbiosis through microbiota transplantation. The noteworthy point is that different methods such as fecal microbiota transplantation, vaginal microbiota transplantation (VMT), skin microbiota transplantation (SMT), oral microbiota transplantation (OMT), washed microbiota transplantation (WMT), and sinonasal microbiota transplantation (SiMT) are used for microbiota transplantation (MT). According to the results of studies and the usefulness of MT in improving a person's health, the purpose of this study is to investigate different methods of MT to eliminate dysbiosis.

Keywords:  Dysbiosis; FMT; MT; Microbiota; OMT; SMT; SiMT; VMT; WMT

DOI:  https://doi.org/10.1016/j.heliyon.2024.e39047
Biofilm. 2024 Dec;8 100237

Small cyclic dipeptide produced by Lactobacillus rhamnosus with anti-biofilm properties against Streptococcus mutans biofilm.

Rashmi Niranjan, Sachin Patil, Amrita Dubey, Bimlesh Lochab, Richa Priyadarshini.

  The human oral cavity harbors many bacterial species collectively termed the oral microbiome and is integral for maintaining oral health. Dysbiosis of oral microbiota leads to common oral diseases, including dental caries, gingivitis, and periodontitis. Streptococcus mutans is the primary causative agent of dental caries. Studies have explored the use of probiotic Lactobacillus spp. to mitigate S. mutans biofilms. In the present study, we have tested the use of Lactobacillus rhamnosus extracts/metabolites for anti-biofilm properties. A small organic compound/metabolite was isolated from the cell-free supernatant of L. rhamnosus, and this metabolite resulted in a dose-dependent inhibition of S. mutans biofilms. Confocal microscopy revealed that the thickness of S. mutans biofilms was severely reduced upon metabolite treatment. With the help of FTIR spectra and mass spectrometry analysis, the molecular formula (C11H19O2N2) was deduced. The inhibitor compound was further identified as a small cyclic peptide, cyclo (-L-Leu-L-Pro). Our data also revealed that isolated metabolite impedes S. mutans biofilms by modulating gene expression of several essential genes involved in biofilm establishment.

Keywords:  Biofilm; Cyclo(-leu-pro); Lactobacillus rhamnosus; Streptococcus mutans, cyclic peptide

DOI:  https://doi.org/10.1016/j.bioflm.2024.100237
Pediatrics. 2024 Dec 01. 154(Suppl 4): S8-S9

The Skin Microbiome in the First Year of Life and Its Association With Atopic Dermatitis.

Stuart L Abramson.

DOI: https://doi.org/10.1542/peds.2024-069114DC
Int Immunopharmacol. 2024 Dec 02. pii: S1567-5769(24)02237-9. [Epub ahead of print]144 113715

Macrophage polarization in sepsis: Emerging role and clinical application prospect.

Fei Fei Hou, Jun Hao Mi, Qiong Wang, Yan Lin Tao, Shuai Bin Guo, Guang He Ran, Jing Chao Wang.

  Sepsis is a severe, potentially fatal condition defined by organ dysfunction due to excessive inflammation. Its complex pathogenesis and poor therapeutic outcomes pose significant challenges in treatment. Macrophages, with their high heterogeneity and plasticity, play crucial roles in both the innate and adaptive immune systems. They can polarize into M1-like macrophages, which promote pro-inflammatory responses, or M2-like macrophages, which mediate anti-inflammatory responses, positioning them as critical mediators in the immune response during sepsis.Macrophages are the main regulators of inflammatory responses, and their polarization is also regulated by inflammatory signaling pathways. This review highlights recent advances in the inflammatory signaling pathways involved in sepsis, mechanism of macrophage polarization mediated by inflammation-related signaling pathways in sepsis, and the role of signaling pathway mediated macrophage polarization in organ dysfunction involved in sepsis. We also explore the therapeutic potential of targeting macrophage polarization for immunotherapy, offering new perspectives on macrophage-targeted treatments for sepsis.

Keywords:  Cellular immunotherapy; Macrophages; Macrophages polarization; Sepsis

DOI:  https://doi.org/10.1016/j.intimp.2024.113715
Cell Death Discov. 2024 Dec 02. 10(1): 485

Infection of Helicobacter pylori contributes to the progression of gastric cancer through ferroptosis.

Yun Liu, Renjie Miao, Jinxuan Xia, Yong Zhou, Jun Yao, Shihe Shao.

Helicobacter pylori (H. pylori) is a gram-negative pathogen that colonizes gastric epithelial cells, and its chronic infection is the primary risk factor for the development of gastric cancer (GC). Ferroptosis is an iron-dependent form of cell death characterized by intracellular lipid peroxide accumulation and reactive oxygen species (ROS) imbalance. There is evidence suggesting that pathogens can manipulate ferroptosis to facilitate their replication, transmission, and pathogenesis. However, the interaction between ferroptosis and H. pylori infection requires further elucidation. We reviewed the mechanism of ferroptosis and found that H. pylori virulence factors such as cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA), neutrophil-activating protein A (NapA), superoxide dismutase B (SodB), γ-glutamyl transpeptidase (gGT), lipopolysaccharide (LPS), and outer inflammatory protein A (OipA) affected glutathione (GSH), ROS, and lipid oxidation to regulate ferroptosis. It also affected the progression of GC by regulating ferroptosis-related indicators through abnormal gene expression after H. pylori infected gastric mucosa cells. Finally, we discuss the potential application value of ferroptosis inducers, inhibitors and other drugs in treating H. pylori-infected GC patients while acknowledging that their interactions are still not fully understood.

DOI: https://doi.org/10.1038/s41420-024-02253-3
J Mol Cell Cardiol. 2024 Nov 29. pii: S0022-2828(24)00200-1. [Epub ahead of print]198 24-35

Hyaluronan provokes inflammation but suppresses phagocytotic function in macrophages.

Timothy N Audam, Caitlin M Howard, Danielle T Little, Lauren F Garrett, Yi Wei Zheng, Zhen Gu, Kenneth R Brittian, Raéden Gray, Julia Chariker, Richa A Singhal, Marcin Wysoczynski, Steven P Jones.

   BACKGROUND: The extracellular matrix (ECM) provides structural and functional support for the myocardium, but myocardial infarction (MI) changes the composition of the ECM. One of the chief components of the ECM, hyaluronan (HA), accumulates after MI; however, specific biological actions of HA-particularly at the level of infiltrating immune cells and implications of such interactions on ventricular remodeling-have not been explored.
GOAL: Because acute accumulation of HA coincides with macrophage infiltration after MI, we assessed the impact of HA on macrophage function.
RESULTS: Compared to SHAM hearts, HA levels were elevated in both the infarct and remote regions of infarcted hearts. Because acute accumulation of HA coincides with macrophage infiltration after MI, we explored the implication of HA accumulation on various endpoints of macrophage function, including macrophage activation, phagocytosis, and efferocytosis. Our data suggests that exposing macrophages to HAHMW pushes macrophages toward a more pro-inflammatory phenotype as indicated by increased secretion of pro-inflammatory signals such as IL-2, IL-17, and IP-10. Our data also suggests that in the presence of HA, both macrophage efferocytosis and Fc-receptor dependent phagocytosis are suppressed. These results are unique to treatment with HAHMW, as similar results were not observed when cells were treated with HALMW. Using macrophages from Cd44-/- mice, we determined that while the impact of HAHMW on cytokine secretion does seem to be dependent in part on Cd44 expression, the impact on macrophage phagocytosis is independent. Since macrophage efferocytosis of dying cardiomyocytes and cellular debris is critical following MI, we believe that this response will prolong the resolution of inflammation and lead to maladaptive remodeling.
CONCLUSION: HA accumulates post-MI and may promote a pro-inflammatory phenotype in macrophages. Future studies will explore the extent to which post infarct HA accumulation regulates cardiac macrophage dynamics and function in vivo.

Keywords:  Efferocytosis; Extracellular matrix; Immune cells; Phagocytosis

DOI:  https://doi.org/10.1016/j.yjmcc.2024.11.009
Exp Dermatol. 2024 Dec;33(12): e70019

Advances in Microbiome-Based Therapeutics for Dermatological Disorders: Current Insights and Future Directions.

Tushar Madaan, Kyla Doan, Alexandra Hartman, Dominick Gherardini, Alec Ventrola, Yuhang Zhang, Nalinikanth Kotagiri.

  The human skin hosts an estimated 1000 bacterial species that are essential for maintaining skin health. Extensive clinical and preclinical studies have established the significant role of the skin microbiome in dermatological disorders such as atopic dermatitis, psoriasis, diabetic foot ulcers, hidradenitis suppurativa and skin cancers. In these conditions, the skin microbiome is not only altered but, in some cases, implicated in disease pathophysiology. Microbiome-based therapies (MBTs) represent an emerging category of live biotherapeutic products with tremendous potential as a novel intervention platform for skin diseases. Beyond using established wild-type strains native to the skin, these therapies can be enhanced to express targeted therapeutic molecules, offering more tailored treatment approaches. This review explores the role of the skin microbiome in various common skin disorders, with a particular focus on the development and therapeutic potential of MBTs for treating these conditions.

Keywords:  acne vulgaris; atopic dermatitis; diabetic foot disease; hidradenitis suppurativa; microbiome‐based therapeutics; psoriasis; skin cancer; skin microbiome

DOI:  https://doi.org/10.1111/exd.70019
Science. 2024 Dec 06. 386(6726): eadp2974

Imperfect wound healing sets the stage for chronic diseases.

Paul Martin, Carlos Pardo-Pastor, R Gisli Jenkins, Jody Rosenblatt.

Although the age of the genome gave us much insight about how our organs fail with disease, it also suggested that diseases do not arise from mutations alone; rather, they develop as we age. In this Review, we examine how wound healing might act to ignite disease. Wound healing works well when we are younger, repairing damage from accidents, environmental assaults, and battles with pathogens. Yet, with age and accumulation of mutations and tissue damage, the repair process can devolve, leading to inflammation, fibrosis, and neoplastic signaling. We discuss healthy wound responses and how our bodies might misappropriate these pathways in disease. Although we focus predominantly on epithelial-based (lung and skin) diseases, similar pathways might operate in cardiac, muscle, and neuronal diseases.

DOI: https://doi.org/10.1126/science.adp2974
MedComm (2020). 2024 Dec;5(12): e70024

Programmed cell death: molecular mechanisms, biological functions, diseases, and therapeutic targets.

Shen'er Qian, Yao Long, Guolin Tan, Xiaoguang Li, Bo Xiang, Yongguang Tao, Zuozhong Xie, Xiaowei Zhang.

  Programmed cell death represents a precisely regulated and active cellular demise, governed by a complex network of specific genes and proteins. The identification of multiple forms of programmed cell death has significantly advanced the understanding of its intricate mechanisms, as demonstrated in recent studies. A thorough grasp of these processes is essential across various biological disciplines and in the study of diseases. Nonetheless, despite notable progress, the exploration of the relationship between programmed cell death and disease, as well as its clinical application, are still in a nascent stage. Therefore, further exploration of programmed cell death and the development of corresponding therapeutic methods and strategies holds substantial potential. Our review provides a detailed examination of the primary mechanisms behind apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. Following this, the discussion delves into biological functions and diseases associated dysregulated programmed cell death. Finally, we highlight existing and potential therapeutic targets and strategies focused on cancers and neurodegenerative diseases. This review aims to summarize the latest insights on programmed cell death from mechanisms to diseases and provides a more reliable approach for clinical transformation.

Keywords:  cancers; cell homeostasis; clinical transformation; neurodegenerative disorders; programmed cell death

DOI:  https://doi.org/10.1002/mco2.70024
Nature. 2024 Dec 04.

How to ensure only dying cells rupture.

Elliott M Bernard, Petr Broz.



Keywords:  Cell biology; Immunology

DOI:  https://doi.org/10.1038/d41586-024-03851-y
Infect Genet Evol. 2024 Nov 29. pii: S1567-1348(24)00144-8. [Epub ahead of print]126 105693

Prevalence and molecular epidemiology of methicillin-resistant Staphylococcus aureus in livestock farmers, livestock, and livestock products in southern Sri Lanka: A one health approach.

M R P Kurukulasooriya, L G Tillekeratne, W M D G B Wijayaratne, C K Bodinayake, U H B Y Dilshan, A D De Silva, B P Nicholson, T Østbye, C W Woods, A De S Nagahawatte.

  Methicillin-resistant Staphylococcus aureus (MRSA) colonization can lead to subsequent severe infections. Unlike community and hospital-associated types, Livestock-associated MRSA (LA-MRSA) transmits to humans through direct contact with livestock and contaminated livestock products. This study aimed to investigate MRSA prevalence and molecular epidemiology in livestock farmers, livestock, and livestock products, including LA-MRSA presence and MRSA abundance in human and animal nasal microbiome, in southern Sri Lanka using a One Health approach. Nasal swabs from farmers and livestock on 50 farms (Nov 2020 - Dec 2021) and livestock products were collected. MRSA was isolated and confirmed using standard microbiological techniques. Staphylococcal chromosomal cassette mec typing, spa typing, and multilocus sequence typing were performed. Identified clones were compared with hospital isolates. Metagenomics analysis was performed on selected samples. MRSA prevalence was 24.0 % (12/50) in farms, 7.9 % (12/152) in farmers, 2.1 % (5/240) in livestock, and 1.9 % (3/157) in products. Of 372 S. aureus collected from clinical cultures, 59.4 % were MRSA. MRSA clones were identified in farm personnel (CC5/ST5/t002, CC1/ST1/t127, and ST45/CC45/t026), livestock (CC5/ST5/t002), and clinical cultures (CC5/ST5/t002 and CC5/ST6/t304), with ST45/CC45/t026 and CC5/ST6/t304 reported for the first time in Sri Lanka. LA-MRSA clones (ST389/ST9) were not detected. Animals had more diverse nasal microbiomes and lower MRSA abundance (<1.4 %) compared to humans (>82.3 %). MRSA colonization prevalence in southern Sri Lanka was relatively low. Two new clones and no LA-MRSA clones were identified. This study highlights the importance of continuing MRSA surveillance under the One Health framework to identify MRSA transmission between humans, animals, and the environment.

Keywords:  LA-MRSA; MRSA prevalence; Molecular epidemiology; Nasal microbiome; One health; Southern Sri Lanka

DOI:  https://doi.org/10.1016/j.meegid.2024.105693
Int Forum Allergy Rhinol. 2024 Dec 03.

Nasal Mucus Cytokines Are Correlated with Spirometry Measures in CRS Patients with Comorbid Asthma.

Rory J Lubner, Christina Dorismond, Mason Krysinski, Ping Li, Rakesh K Chandra, Justin H Turner, Dawn C Newcomb, Katherine N Cahill, Naweed I Chowdhury.

   KEY POINTS: CRS patients with asthma show differential nasal mucus cytokine signatures based on endotype. IL-7 concentration is positively associated with higher %FEV1 and %FVC in CRS patients with asthma.

Keywords:  asthma; chronic rhinosinusitis; cytokine; endoscopic sinus surgery

DOI:  https://doi.org/10.1002/alr.23492
Cell Prolif. 2024 Dec 03. e13779

Ferroptosis in Osteoarthritis: Towards Novel Therapeutic Strategy.

Yiming Zhang, Jing Li, Jiane Liu, Yan Gao, Kehan Li, Xinyu Zhao, Yufeng Liu, Daijie Wang, Xiao Hu, Zheng Wang.

  Osteoarthritis (OA) is a chronic, degenerative joint disease primarily characterised by damage to the articular cartilage, synovitis and persistent pain, and has become one of the most common diseases worldwide. In OA cartilage, various forms of cell death have been identified, including apoptosis, necroptosis and autophagic cell death. Ever-growing observations indicate that ferroptosis, a newly-discovered iron-dependent form of regulated cell death, is detrimental to OA occurrence and progression. In this review, we first analyse the pathogenetic mechanisms of OA by which iron overload, inflammatory response and mechanical stress contribute to ferroptosis. We then discuss how ferroptosis exacerbates OA progression, focusing on its impact on chondrocyte viability, synoviocyte populations and extracellular matrix integrity. Finally, we highlight several potential therapeutic strategies targeting ferroptosis that could be explored for the treatment of OA.

Keywords:  ferroptosis; mechanism; osteoarthritis; therapeutic strategy

DOI:  https://doi.org/10.1111/cpr.13779
Nat Rev Immunol. 2024 Dec 03.

Guardians of immune privilege.

Yvonne Bordon.

DOI: https://doi.org/10.1038/s41577-024-01121-6
Pediatr Res. 2024 Nov 30.

Comparison of nasal microbiota between preterm and full-term infants in early life.

BILD study consortium

BACKGROUND: The respiratory microbiota influences infant immune system maturation. Little is known about how perinatal, physiological, and environmental exposures impact the nasal microbiota in preterm infants after discharge, or nasal microbiota differences between preterm and healthy full-term infants.
METHODS: Nasal swabs (from 136 preterm and 299 full-term infants at mean postmenstrual age of 45 weeks from the prospective Basel-Bern Infant Lung Development cohort) were analyzed by 16S-rRNA gene amplification and sequencing (Illumina MiSeq). Associations were tested with multivariable linear regression and principal coordinate analysis.
RESULTS: Presence of older siblings in preterm infants was associated with β-diversity (PERMANOVA p = 0.001) and an increased abundance of Moraxella and Haemophilus. The nasal microbiota of preterm infants exhibited a distinct composition compared to that of full-term infants (PERMANOVA, R2 = 0.014, p = 0.001), characterized by a reduced abundance of the Moraxella and Dolosigranulum genera (ANCOM-BC, p < 0.05).
CONCLUSION: Our results indicate that, despite both infant groups having similar nasal microbiota patterns, there are some disparities which suggest that prematurity influences the initial microbiota colonization. In preterm infants the presence of older siblings had an effect on the nasal microbiota, whereas perinatal and early postnatal factors did not show significant effects.
IMPACT: Presence of older siblings affected the nasal microbiota of preterm infants. This study demonstrated that microbiota composition differs between full-term and preterm infants, with a lower abundance of Moraxella and Dolosigranulum in preterm infants. Examining the differences in nasal microbiota between preterm and full-term infants may contribute to understanding the trajectory of the bacterial component of the nasal microbiota of preterm infants.

DOI: https://doi.org/10.1038/s41390-024-03675-6