bims-bac4me 2024-12-22 papers

bims-bac4me

Biomed News

on Microbiome and trained immunity

Issue of 2024–12–22
24 papers selected by
Chun-Chi Chang, Universitäts Spital Zürich

Human airway epithelium controls Pseudomonas aeruginosa infection via inducible nitric oxide synthase.
Protective effect of interferon type I on barrier function of human airway epithelium during rhinovirus infections in vitro.
Mucosal Inflammatory Memory in Chronic Rhinosinusitis.
Skin-associated Corynebacterium amycolatum shares cobamides.
Interleukin 10 drives Staphylococcus aureus imprinting and vaccine failure in murine models via antibody glycosylation.
Staphylococcus aureus regulates Th17 cells and autophagy via STING in chronic eosinophilic rhinosinusitis with nasal polyps.
Introduction to immunology and immune disorders.
Pathobiont-driven antibody sialylation through IL-10 undermines vaccination.
Author Correction: Examining the healthy human microbiome concept.
Author Correction: Immunological memory diversity in the human upper airway.
The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation.
Immunomodulatory potential of primary cilia in the skin.
Link between respiratory microbiota and asthma: an emerging therapeutic approach.
GPx1 deficiency confers increased susceptibility to ferroptosis in macrophages from individuals with active Crohn's disease.
CD226 + adipose tissue macrophages arise from MDP-derived monocytes and regulate lipid metabolism.
Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses.
Protocol to phenotype and quantify mycobacteria-specific myeloid cells from human airways by mass cytometry.
How the early life microbiome shapes immune programming in childhood asthma and allergies.
A cholesterol metabolite against ferroptosis.
Transcriptome analyses of mRNA and circular RNA reveal dietary supplementation with freeze-dried Lactiplantibacillus plantarum primes immune memory of Whiteleg shrimp (Penaeus vannamei) against pathogens.
Class B Scavenger Receptor CD36 as a Potential Therapeutic Target in Inflammation Induced by Danger-Associated Molecular Patterns.
Advancing microbiota therapeutics: the role of synthetic biology in engineering microbial communities for precision medicine.
Crosstalk between lactate and tumor-associated immune cells: clinical relevance and insight.
Targeting quorum sensing for manipulation of commensal microbiota.

Front Immunol. 2024 ;15 1508727

Human airway epithelium controls Pseudomonas aeruginosa infection via inducible nitric oxide synthase.

Philipp Grubwieser, Nina Böck, Erika Kvalem Soto, Richard Hilbe, Patrizia Moser, Markus Seifert, Stefanie Dichtl, Miriam Alisa Govrins, Wilfried Posch, Thomas Sonnweber, Manfred Nairz, Igor Theurl, Zlatko Trajanoski, Günter Weiss.

   Introduction: Airway epithelial cells play a central role in the innate immune response to invading bacteria, yet adequate human infection models are lacking.
Methods: We utilized mucociliary-differentiated human airway organoids with direct access to the apical side of epithelial cells to model the initial phase of Pseudomonas aeruginosa respiratory tract infection.
Results: Immunofluorescence of infected organoids revealed that Pseudomonas aeruginosa invades the epithelial barrier and subsequently proliferates within the epithelial space. RNA sequencing analysis demonstrated that Pseudomonas infection stimulated innate antimicrobial immune responses, but specifically enhanced the expression of genes of the nitric oxide metabolic pathway. We demonstrated that activation of inducible nitric oxide synthase (iNOS) in airway organoids exposed bacteria to nitrosative stress, effectively inhibiting intra-epithelial pathogen proliferation. Pharmacological inhibition of iNOS resulted in expansion of bacterial proliferation whereas a NO producing drug reduced bacterial numbers. iNOS expression was mainly localized to ciliated epithelial cells of infected airway organoids, which was confirmed in primary human lung tissue during Pseudomonas pneumonia.
Discussion: Our findings highlight the critical role of epithelial-derived iNOS in host defence against Pseudomonas aeruginosa infection. Furthermore, we describe a human tissue model that accurately mimics the airway epithelium, providing a valuable framework for systemically studying host-pathogen interactions in respiratory infections.

Keywords:  Pseudomonas aeruginosa; airway epithelia; airway organoids; iNOS; innate immunity

DOI:  https://doi.org/10.3389/fimmu.2024.1508727
Sci Rep. 2024 12 16. 14(1): 30510

Protective effect of interferon type I on barrier function of human airway epithelium during rhinovirus infections in vitro.

Helena Boland, Adrian Endres, Ralf Kinscherf, Ralf Schubert, Beate Wilhelm, Hans Schwarzbach, Danny Jonigk, Peter Braubach, Gernot Rohde, Carla Bellinghausen.

The airway epithelium provides a crucial barrier against infection with respiratory pathogens. This barrier can be impaired following viral infection, paving the way for bacterial superinfections. Type I interferons (IFNs) are important antiviral mediators, and inhaled formulations of these glycoproteins are considered a potential approach for the treatment of respiratory viral infections. To investigate if type I IFNs can also protect against virus-induced epithelial barrier dysfunction, differentiated primary bronchial epithelial cells were pre-treated with IFN-β1a and subsequently infected with human rhinovirus (HRV) for 24 to 72h. Moreover, to functionally assess the effects of IFN-β1a pre-treatment on barrier integrity, we conducted co-infection experiments, in which cells were initially infected with HRV, and superinfected with Streptococcus pneumoniae 24 to 72 h later. In untreated cells, HRV infection significantly damaged ZO-1 positive tight junctions and cilia, and transiently increased permeability, whereas the barrier of cultures pre-treated with IFN-β1a remained intact. In co-infection experiments, bacteria were able to penetrate deeper into the cell layers of HRV-infected cultures than into those of uninfected cells. IFN-β1a pre-treatment abrogated virus-induced damage to the epithelial barrier. Taken together, these data demonstrate a beneficial effect of IFN-β in protecting epithelial barrier function in addition to its antiviral effects.

DOI: https://doi.org/10.1038/s41598-024-82516-2
Cells. 2024 Nov 23. pii: 1947. [Epub ahead of print]13(23):

Mucosal Inflammatory Memory in Chronic Rhinosinusitis.

Min-Seok Koo, Sungmin Moon, Min-Seok Rha.

  Recent advancements in medical management, endoscopic sinus surgery, and biologics have significantly improved outcomes for patients with chronic rhinosinusitis (CRS). However, long-term recurrence is frequently observed following endoscopic sinus surgery, with symptoms worsening after biologics are discontinued. Consequently, refractory or recurrent CRS remains a significant challenge, causing a substantial healthcare burden. In this review, we provide current insights into mucosal inflammatory memory, a potential mechanism leading to CRS recurrence. Given that both immune and non-immune cells in the sinonasal mucosa play critical roles in the pathophysiology of CRS, a deeper understanding of the mechanisms underlying mucosal inflammatory memory in various cellular components of sinonasal tissue could aid in the management of refractory CRS. We describe and discuss the latest knowledge regarding the novel concept of inflammatory memory, including both adaptive immune memory and trained immunity. Additionally, we summarize the pathogenic memory features of the sinonasal mucosa cellular components in the context of CRS.

Keywords:  chronic rhinosinusitis; inflammatory memory; mucosal immunity; trained immunity

DOI:  https://doi.org/10.3390/cells13231947
mSphere. 2024 Dec 18. e0060624

Skin-associated Corynebacterium amycolatum shares cobamides.

M H Swaney, N Henriquez, T Campbell, J Handelsman, L R Kalan.

  The underlying interactions that occur to maintain skin microbiome composition, function, and overall skin health are largely unknown. Often, these types of interactions are mediated by microbial metabolites. Cobamides, the vitamin B12 family of cofactors, are essential for metabolism in many bacteria but are only synthesized by a fraction of prokaryotes, including certain skin-associated species. Therefore, we hypothesize that cobamide sharing mediates skin community dynamics. Preliminary work predicts that several skin-associated Corynebacterium species encode de novo cobamide biosynthesis and that their abundance is associated with skin microbiome diversity. Here, we show that commensal Corynebacterium amycolatum produces cobamides and that this synthesis can be tuned by cobalt limitation. To demonstrate cobamide sharing by C. amycolatum, we employed a co-culture assay using an E. coli cobamide auxotroph and showed that C. amycolatum produces sufficient cobamides to support Escherichia coli growth, both in liquid co-culture and when separated spatially on solid medium. We also generated a C. amycolatum non-cobamide-producing strain (cob-) using UV mutagenesis that contains mutated cobamide biosynthesis genes cobK (precorrin-6X reductase) and cobO (corrinoid adenosyltransferase) and confirm that disruption of cobamide biosynthesis abolishes the support of E. coli growth through cobamide sharing. Our study provides a unique model to study metabolite sharing by microorganisms, which will be critical for understanding the fundamental interactions that occur within complex microbiomes and for developing approaches to target the human microbiota for health advances.
IMPORTANCE: The human skin serves as a crucial barrier for the body and hosts a diverse community of microbes known as the skin microbiome. The interactions that occur to maintain a healthy skin microbiome are largely unknown but are thought to be driven in part, by nutrient sharing between species in close association. Here we show that the skin-associated bacteria Corynebacterium amycolatum produces and shares cobalamin, a cofactor essential for survival in organisms across all domains of life. This study provides a unique model to study metabolite sharing by skin microorganisms, which will be critical for understanding the fundamental interactions that occur within the skin microbiome and for developing therapeutic approaches aiming to engineer and manipulate the skin microbiota.

Keywords:  cobamide; corynebacterium; nutrient sharing; skin microbiome

DOI:  https://doi.org/10.1128/msphere.00606-24
J Clin Invest. 2024 Dec 16. pii: e187055. [Epub ahead of print]134(24):

Interleukin 10 drives Staphylococcus aureus imprinting and vaccine failure in murine models via antibody glycosylation.

Victor J Torres.

Despite many attempts, there is currently no approved vaccine to prevent Staphylococcus aureus infections. Preclinical vaccination models have failed to predict vaccine efficacy in humans as S. aureus exposure in humans imprints an immune response that is lacking in naive animals. In this issue of the JCI, Tsai and colleagues identify the cytokine IL-10 as the driver of humoral imprinting by S. aureus. Upon vaccination, S. aureus-experienced animals produced copious levels of IL-10, resulting in the hyper-α2,3 sialylation of antibodies, which interfered with the phagocytic-promoting properties of the vaccine-elicited anti-S. aureus antibodies. These findings correlate with the observation that hyperproduction of IL-10 in humans also induces hyper-α2,3 sialylation of antibodies and provide a possible mechanism for previous vaccine failures.

DOI: https://doi.org/10.1172/JCI187055
Eur Arch Otorhinolaryngol. 2024 Dec 14.

Staphylococcus aureus regulates Th17 cells and autophagy via STING in chronic eosinophilic rhinosinusitis with nasal polyps.

Weigang Gan, Xingchen Liu, Feng Liu, Junying Hu.

   PURPOSE: As a common pathogen of rhinosinusitis, the role of Staphylococcus aureus in modulating autophagy through STING activation and Th17 cell differentiation in CRSwNP remains unexplored. This study aims to investigate how S. aureus regulates Th17 cell differentiation and the occurrence and development of autophagy in CRS by inducing STING expression.
METHODS: Immunoblotting and flow cytometry were employed to assess the expression levels of STING, RORγt, LC3B, and MUC5AC, as well as Th17 markers in cells. HNECs were co-cultured with S. aureus in vitro to explore its regulatory effects.
RESULTS: STING expression was found to be decreased in CRSwNP tissues, while RORγt, LC3B, and MUC5AC levels were elevated. S. aureus was shown to induce Th17 differentiation via STING regulation. STING activators reduced Th17 inflammation, while autophagy activators increased autophagosomes and MUC5AC levels.
CONCLUSION: The STING system may play a protective role in the inflammatory response of nasal epithelial cells. S. aureus inhibits STING, not only by promoting the differentiation of pathogenic Th17 cells but also by increasing autophagy levels in nasal epithelial cells. Both mechanisms contribute to the enhanced expression of MUC5AC, facilitating the progression of CRSwNP.

Keywords:  Autophagy; CRSwNP; STING; Staphylococcus aureus; Th17

DOI:  https://doi.org/10.1007/s00405-024-09100-2
Allergy Asthma Clin Immunol. 2024 Dec 19. 20(Suppl 3): 69

Introduction to immunology and immune disorders.

Jean S Marshall, Julia E M Upton, Harissios Vliagoftis, Kyla J Hildebrand, Adam Byrne, Wade Watson.

The body has a collection of physical barriers to prevent infection, but once these are overcome, we rely on our immune systems to protect us against a wide variety of infections. The complex mechanisms through which this is achieved are grouped into two lines of defense called the "innate" and "adaptive" immune systems. The innate immune system provides a rapid and tailored response to infection or injury often associated with inflammation. Innate immunity also promotes the development of acquired immunity. Specific, long-lasting responses against a particular infection are dependent on acquired immunity, and these provide immune memory, such that if we encounter the same pathogen again, we are better protected. Many diseases are related to defects in immune function which can lead to either a weakened or overactive immune response. Autoimmune diseases (where the immune system attacks tissues or organs) and allergies (where the immune system responds inappropriately to substances in our environment) are just two examples of conditions resulting from immune function defects. Improved understanding of immune processes provides tremendous opportunities for enhanced immunization strategies and immune-based therapies. This article provides an overview of the main components and functions of the immune system, and also serves as a primer to help readers understand the immunopathological disorders discussed in the remainder of this supplement.

DOI: https://doi.org/10.1186/s13223-024-00932-5
J Clin Invest. 2024 Dec 16. pii: e179563. [Epub ahead of print]134(24):

Pathobiont-driven antibody sialylation through IL-10 undermines vaccination.

Chih-Ming Tsai, Irshad A Hajam, J R Caldera, Austin Wt Chiang, Cesia Gonzalez, Xin Du, Biswa Choudhruy, Haining Li, Emi Suzuki, Fatemeh Askarian, Ty'Tianna Clark, Brian Lin, Igor H Wierzbicki, Angelica M Riestra, Douglas J Conrad, David J Gonzalez, Victor Nizet, Nathan E Lewis, George Y Liu.

  The pathobiont Staphylococcus aureus (Sa) induces nonprotective antibody imprints that underlie ineffective staphylococcal vaccination. However, the mechanism by which Sa modifies antibody activity is not clear. Herein, we demonstrate that IL-10 is the decisive factor that abrogates antibody protection in mice. Sa-induced B10 cells drive antigen-specific vaccine suppression that affects both recalled and de novo developed B cells. Released IL-10 promotes STAT3 binding upstream of the gene encoding sialyltransferase ST3gal4 and increases its expression by B cells, leading to hyper-α2,3sialylation of antibodies and loss of protective activity. IL-10 enhances α2,3sialylation on cell-wall-associated IsdB, IsdA, and MntC antibodies along with suppression of the respective Sa vaccines. Consistent with mouse findings, human anti-Sa antibodies as well as anti-pseudomonal antibodies from cystic fibrosis subjects (high IL-10) are hypersialylated, compared with anti-Streptococcus pyogenes and pseudomonal antibodies from normal individuals. Overall, we demonstrate a pathobiont-centric mechanism that modulates antibody glycosylation through IL-10, leading to loss of staphylococcal vaccine efficacy.

Keywords:  Adaptive immunity; Immunology; Imprinting; Infectious disease

DOI:  https://doi.org/10.1172/JCI179563
Nat Rev Microbiol. 2024 Dec 16.

Author Correction: Examining the healthy human microbiome concept.

Human Microbiome Action Consortium

DOI: https://doi.org/10.1038/s41579-024-01145-8
Nature. 2024 Dec 16.

Author Correction: Immunological memory diversity in the human upper airway.

Sydney I Ramirez, Farhoud Faraji, L Benjamin Hills, Paul G Lopez, Benjamin Goodwin, Hannah D Stacey, Henry J Sutton, Kathryn M Hastie, Erica Ollmann Saphire, Hyun Jik Kim, Sara Mashoof, Carol H Yan, Adam S DeConde, Gina Levi, Shane Crotty.

DOI: https://doi.org/10.1038/s41586-024-08519-1
Gut Microbes. 2024 Jan-Dec;16(1):16(1): 2438829

The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation.

Janire Castelo, Sarai Araujo-Aris, Diego Barriales, Samuel Tanner Pasco, Iratxe Seoane, Ainize Peña-Cearra, Ainhoa Palacios, Carolina Simó, Virginia Garcia-Cañas, Muthita Khamwong, Itziar Martín-Ruiz, Monika Gonzalez-Lopez, Laura Barcena, José Ezequiel Martín Rodríguez, José Luís Lavín, Naiara Gutiez, Raquel Marcos, Estibaliz Atondo, Arantza Cobela, Laura Plaza-Vinuesa, Adrián Plata, Eneko Santos-Fernandez, Alberto Fernandez-Tejada, Mari Carmen Villarán, José Miguel Mancheño, Juana Maria Flores, Ana María Aransay, Aize Pellón, Blanca de Las Rivas, Rosario Muñoz, Abelardo Margolles, Patricia Ruas-Madiedo, Maria Victoria Selma, Mercedes Gomez de Agüero, Leticia Abecia, Juan Anguita, Héctor Rodríguez.

  Phloroglucinol is a key byproduct of gut microbial metabolism that has been widely used as a treatment for irritable bowel syndrome. Here, we demonstrate that phloroglucinol tempers macrophage responses to pro-inflammatory pathogens and stimuli. In vivo, phloroglucinol administration decreases gut and extraintestinal inflammation in murine models of inflammatory bowel disease and systemic infection. The metabolite induces modest modifications in the microbiota. However, the presence of an active microbiota is required to preserve its anti-inflammatory activity. Remarkably, the protective effect of phloroglucinol lasts partially at least 6 months. Single-cell transcriptomic analysis of bone marrow progenitors demonstrates the capacity of the metabolite to induce long-lasting innate immune training in hematopoietic lineages, at least partially through the participation of the receptor and transcription factor, aryl hydrocarbon receptor (AhR). Phloroglucinol induces alterations in metabolic and epigenetic pathways that are most prevalent in upstream progenitors as hallmarks of central trained immunity. These data identify phloroglucinol as a dietary-derived compound capable of inducing central trained immunity and modulating the response of the host to inflammatory insults.

Keywords:  Microbiota byproducts; central trained immunity; inflammation; phenolic derivatives

DOI:  https://doi.org/10.1080/19490976.2024.2438829
Front Immunol. 2024 ;15 1456875

Immunomodulatory potential of primary cilia in the skin.

Jingwei Sun, Huimin Yuan, Yanru Yu, Aorou Li, Zihe Zhao, Yang Tang, Fengjie Zheng.

  Primary cilia (PC) are essential signaling hubs for proper epithelial formation and the maintenance of skin homeostasis. Found on most cells in the human body, including skin cells, PC facilitate signal transduction that allows ciliated cells to interact with the immune system via multiple pathways, helping to maintain immune system homeostasis. PC can be altered by various microenvironmental stimuli to develop corresponding regulatory functions. Both PC and ciliary signaling pathways have been shown to be involved in the immune processes of various skin lesions. However, the mechanisms by which PC regulate cellular functions and maintain immune homeostasis in tissues are highly complex, and our understanding of them in the skin remains limited. In this paper, we discuss key ciliary signaling pathways and ciliated cells in the skin, with a focus on their immunomodulatory functions. We have compiled evidence from various cells, tissues and disease models to help explore the potential immunomodulatory effects of PC in the skin and their molecular mechanisms.

Keywords:  Langerhans cells; fibroblasts; immunoregulation; keratinocytes; primary cilia; signaling pathway; skin

DOI:  https://doi.org/10.3389/fimmu.2024.1456875
Am J Transl Res. 2024 ;16(11): 6289-6302

Link between respiratory microbiota and asthma: an emerging therapeutic approach.

Chunyuan Tian, Xing Li, Xingxing Yuan, Zhuying Li.

  The respiratory microbiota significantly influence the onset and progression of asthma, as underscored by recent studies revealing discernible differences between asthma patients and healthy individuals. This review delves into the relationship between respiratory microbiota and asthma, with a particular emphasis on possible therapeutic targets and emerging treatments. Existing research is thoroughly synthesized, illuminating the association between microbial communities and the incidence of asthma. In addition to antibiotic therapy, attention is directed towards modulating the immune balance within the respiratory microbiota as a promising therapeutic approach. Specifically, the role of immunomodulators targeting key immune pathways, such as interleukins and cytokines implicated in asthma pathogenesis, is examined. Furthermore, the regulation of the gut-lung axis is explored, highlighting the significance of the gut microbiota in shaping systemic immune responses and respiratory health. Moreover, the potential of immune cell modulation as a therapeutic avenue is explored, focusing on targeting specific immune cell populations involved in asthma pathophysiology. Future research directions and challenges are also addressed, underscoring the need for a deeper understanding of the intricate interplay between respiratory microbiota and the pathogenesis of asthma.

Keywords:  Respiratory microbiota; asthma; immune modulation; therapeutic targets

DOI:  https://doi.org/10.62347/OSNZ1705
Cell Death Dis. 2024 Dec 18. 15(12): 903

GPx1 deficiency confers increased susceptibility to ferroptosis in macrophages from individuals with active Crohn's disease.

James A Sousa, Blanca E Callejas, Arthur Wang, Eve Higgins, Aydin Herik, Natalie Andonian, Munazza Yousuf, Pina Colarusso, Maitreyi Raman, Derek M McKay.

Intestinal cell death is a defining feature of Crohn's disease (CD), a major form of inflammatory bowel disease. The focus on this aspect of enteric inflammation has mainly been on epithelial cells, while other cell types such as stromal and myeloid cells have received less attention. Hypothesising that decreased macrophage viability in an oxidative environment could be a contributing factor to the pathophysiology of CD, we found that monocyte-derived macrophages from individuals with active CD (but not those in clinical disease remission) have increased sensitivity to cell death induced by H2O2. Molecular biology and pharmacological studies ruled out apoptosis and necroptosis, while increased lipid peroxidation and surface expression of the transferrin receptor implicated ferroptosis as the mechanism of the H2O2-induced cell death: this was supported by suppression of H2O2-cytotoxicity by liproxstatin-1, a pharmacological inhibitor of ferroptosis. Selenoproteins are important antioxidants, and selenium deficiency can be a feature of CD. Despite normal dietary intake of selenium, monocyte-derived macrophages and intestinal macrophages in individuals with CD had decreased protein and/or mRNA expression of the selenoprotein, glutathione peroxidase (GPx)-1. Knockdown of GPx1 in macrophages from healthy volunteers resulted in increased H2O2-induced cell death reminiscent of that observed with macrophages from CD. In summary, monocyte-derived macrophages from individuals with CD have increased susceptibility to H2O2-induced ferroptosis cell death, that may be facilitated, at least in part, by reduced expression of the antioxidant GPx1. We suggest that reduced GPx1 in monocytes recruited to the gut and intestinal macrophages renders these cells vulnerable to reactive oxygen species-evoked ferroptosis cell death and that unraveling the participation of this pathway in Crohn's disease may reveal novel therapeutic approaches to this chronic condition.

DOI: https://doi.org/10.1038/s41419-024-07289-y
bioRxiv. 2024 Dec 05. pii: 2024.12.03.626330. [Epub ahead of print]

CD226 + adipose tissue macrophages arise from MDP-derived monocytes and regulate lipid metabolism.

Alexandre Gallerand, Zakariya Caillot, Marina Terekhova, Alexia Castiglione, Lorlana Leporati, Margaux Giacchero, Thomas Pilot, Michael Chang, Bastien Dolfi, Fairouz N Zair, Eloïse Goës, Audrey Bennetot, Zandile Mlamla, Elvira Mass, Florent Ginhoux, David Voehringer, Matthias Mack, David Dombrowicz, Jesse W Williams, David Masson, Maxim N Artyomov, Adeline Bertola, Stoyan Ivanov.

Macrophages are innate immune cells present in all tissues, in which they participate in immune responses and maintenance of tissue homeostasis. They develop either from embryonic precursors or from circulating monocytes, and their functions are in part dictated by their origin. We previously observed robust monocyte recruitment and contribution to the macrophage pool in brown adipose tissue. In particular, monocytes were predicted to give rise to two phenotypically distinct macrophage subsets identifiable by CD206 or CD226 expression. In the present study, we investigated monocyte differentiation pathways in brown adipose tissue and the function of monocyte-derived macrophages. We found that bone marrow monocytes highly contributed to the CD226 + macrophage population while the CD206 + population contained mainly yolk sac-derived cells. Fate mapping analysis revealed a low contribution of GMP- and a high contribution of MDP-derived monocytes to the CD226 + macrophage subset. Importantly, adoptive transfer experiments demonstrate that MDP- but not GMP-derived monocytes are pre-conditioned to give rise to CD226 + macrophages. Using meta-analysis of single cell RNA-sequencing data, we found that MDP-derived CD226 + macrophages were present in several tissues including peritoneal cavity, adrenal glands and all adipose depots, with a particular enrichment in beige and brown fat. A similar macrophage subset was identified in humans. Functionally, while depletion of CD206 + macrophages using anti-CD115 blocking antibodies led to decreased adipose triglyceride content, genetic depletion of CD226 + macrophages caused the opposite phenotype. We thus identify CD226 + MDP-derived macrophages as a new myeloid cell type conserved across tissues and tied to lipid metabolism homeostasis.

DOI: https://doi.org/10.1101/2024.12.03.626330
Nat Commun. 2024 Dec 16. 15(1): 10335

Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses.

Irshad Ahmed Hajam, Chih-Ming Tsai, Cesia Gonzalez, Juan Raphael Caldera, María Lázaro Díez, Xin Du, April Aralar, Brian Lin, William Duong, George Y Liu.

Pathobionts have evolved many strategies to coexist with the host, but how immune evasion mechanisms contribute to the difficulty of developing vaccines against pathobionts is unclear. Meanwhile, Staphylococcus aureus (SA) has resisted human vaccine development to date. Here we show that prior SA exposure induces non-protective CD4+ T cell imprints, leading to the blunting of protective IsdB vaccine responses. Mechanistically, these SA-experienced CD4+ T cells express IL-10, which is further amplified by vaccination and impedes vaccine protection by binding with IL-10Rα on CD4+ T cell and inhibit IL-17A production. IL-10 also mediates cross-suppression of IsdB and sdrE multi-antigen vaccine. By contrast, the inefficiency of SA IsdB, IsdA and MntC vaccines can be overcome by co-treatment with adjuvants that promote IL-17A and IFN-γ responses. We thus propose that IL-10 secreting, SA-experienced CD4+ T cell imprints represent a staphylococcal immune escaping mechanism that needs to be taken into consideration for future vaccine development.

DOI: https://doi.org/10.1038/s41467-024-54644-w
STAR Protoc. 2024 Dec 12. pii: S2666-1667(24)00628-2. [Epub ahead of print]5(4): 103463

Protocol to phenotype and quantify mycobacteria-specific myeloid cells from human airways by mass cytometry.

POI-BAL study group

  Alveolar macrophages and other myeloid cells in the human airways are the primary cell types responding to respiratory pathogens. Here, we present a protocol for in vitro stimulation of cryopreserved human bronchoalveolar lavage (BAL) cells with mycobacterial antigens for phenotyping and quantifying proinflammatory cytokine responses in myeloid cells by mass cytometry. We demonstrate that the measure of markers of myeloid lineage and function is stable after freezing stained cells thereby allowing for batched analyses and/or machine downtime.

Keywords:  Cell culture; Immunology; Mass Cytometry

DOI:  https://doi.org/10.1016/j.xpro.2024.103463
Mucosal Immunol. 2024 Dec 13. pii: S1933-0219(24)00128-4. [Epub ahead of print]

How the early life microbiome shapes immune programming in childhood asthma and allergies.

Courtney Hoskinson, Charisse Petersen, Stuart E Turvey.

  Despite advances in our understanding of their diagnosis and treatment, pediatric allergies impose substantial burdens on affected children, families, and healthcare systems. Further, the prevalence of allergic diseases has dramatically increased over the past half-century, leading to additional concerns and concerted efforts to identify the origins, potential predictors and preventions, and therapies of allergic diseases. Together with the increase in allergic diseases, changes in lifestyle and early-life environmental influences have corresponded with changes in colonization patterns of the infant gut microbiome. The gut microbiome plays a key role in developing the immune system, thus greatly influencing the development of allergic disease. In this review, we specifically highlight the importance of the proper maturation and composition of the gut microbiome as an essential step in healthy child development or disease progression. By exploring the intertwined development of the immune system and microbiome across pediatric allergic diseases, we provide insights into potential novel strategies for their prevention and management.

Keywords:  Allergy; Immune development; Microbiome; Sequencing

DOI:  https://doi.org/10.1016/j.mucimm.2024.12.005
Nat Cancer. 2024 Dec 17.

A cholesterol metabolite against ferroptosis.

Julieta Alfonso.

DOI: https://doi.org/10.1038/s43018-024-00849-3
Fish Shellfish Immunol. 2024 Dec 12. pii: S1050-4648(24)00737-X. [Epub ahead of print]157 110091

Transcriptome analyses of mRNA and circular RNA reveal dietary supplementation with freeze-dried Lactiplantibacillus plantarum primes immune memory of Whiteleg shrimp (Penaeus vannamei) against pathogens.

John Paul Matthew Domingo Guzman, Reiko Nozaki, Mikio Aoki, Hiroshi Kuwahara, Kazuki Mikata, Keiichiro Koiwai, Hidehiro Kondo, Ikuo Hirono.

  The lack of a classical adaptive immunity renders the development of disease control and prevention measures in shrimp challenging. In this study, the concept of trained immunity was exploited in the development of a feed supplement. Penaeus vannamei shrimp was fed with feed supplemented with freeze-dried whole culture of Lactiplantibacillus plantarum (FD-LAB) for 15 days. RNA sequencing using Illumina platform was performed on the gill and stomach tissues collected at specific time points during the feeding period (0th day, 8th day, 15th day). Differentially-expressed genes (DEGs) previously reported to have innate immunity- and immune memory-related functions were selected for validation. Additionally, the differential expression of putatively immune-related circular RNAs (DECs) were also explored as these noncoding regulatory RNAs may also influence host immunity. Challenge tests with either the acute hepatopancreatic necrosis disease-causing strain Vibrio parahaemolyticus D6 or White Spot Syndrome Virus (WSSV) were conducted. Transcriptome analyses showed that FD-LAB supplementation resulted to DEGs and DECs related to pathogen recognition, antimicrobial peptides, transcription regulation, and immune memory. Challenge tests performed immediately after 15 days and 8 days of feeding showed protection on P. vannamei by FD-LAB against bacterial and viral pathogens. Increase in survival rates were also observed upon challenge with both pathogens 7 days and 14 days after last intake of FD-LAB, indicating trained immunity in shrimp. Our study highlighted the effects of FD-LAB on the innate immunity and immune memory of P. vannamei against bacterial and viral pathogens. These findings emphasize the possibility of immunostimulants inducing lasting enhanced immunity against infections despite the lack of a classical adaptive immunity in shrimp.

Keywords:  Acute hepatopancreatic necrosis disease; Feed supplement; Immune priming; Lactic acid bacteria; Trained immunity; White spot syndrome virus

DOI:  https://doi.org/10.1016/j.fsi.2024.110091
Cells. 2024 Dec 03. pii: 1992. [Epub ahead of print]13(23):

Class B Scavenger Receptor CD36 as a Potential Therapeutic Target in Inflammation Induced by Danger-Associated Molecular Patterns.

Irina N Baranova, Alexander V Bocharov, Tatyana G Vishnyakova, Zhigang Chen, Yunbo Ke, Anna A Birukova, Peter S T Yuen, Takayuki Tsuji, Robert A Star, Konstantin G Birukov, Amy P Patterson, Thomas L Eggerman.

  The class B scavenger receptor CD36 is known to bind and mediate the transport of lipid-related ligands and it functions as a pattern recognition receptor (PRR) for a variety of pathogens, including bacteria and viruses. In this study, we assessed CD36's role as a PRR mediating pro-inflammatory effects of several known Danger-Associated Molecular Patterns (DAMPs) used either as a single preparation or as a combination of DAMPs in the form of total cell/skeletal muscle tissue lysates. Our data demonstrated that multiple DAMPs, including HMGB1, HSPs, histone H3, SAA, and oxPAPC, as well as cell/tissue lysate preparations, induced substantially higher (~7-10-fold) IL-8 cytokine responses in HEK293 cells overexpressing CD36 compared to control WT cells. At the same time, DAMP-induced secretion of IL-6 in bone marrow-derived macrophages (BMDM) from CD36-/- mice was markedly (~2-3 times) reduced, as compared to macrophages from normal mice. Synthetic amphipathic helical peptides (SAHPs), known CD36 ligands, efficiently blocked CD36-dependent inflammatory responses induced by both cell and tissue lysates, HMGB1 and histone H3 in CD36+ cells. IP injection of total cellular lysate preparation induced inflammatory responses that were assessed by the expression of liver and lung pro-inflammatory markers, including IL-6, TNF-α, CD68, and CXCL1, and was reduced by ~50% in CD36-deficient mice compared to normal mice. Our findings demonstrate that CD36 is a PRR contributing to the innate immune response via mediating DAMP-induced inflammatory signaling and highlight the importance of this receptor as a potential therapeutic target in DAMP-associated inflammatory conditions.

Keywords:  CD36; DAMPs; HMGB1; SAA; heat shock proteins; histones; inflammatory markers; oxPAPC

DOI:  https://doi.org/10.3390/cells13231992
Front Bioeng Biotechnol. 2024 ;12 1511149

Advancing microbiota therapeutics: the role of synthetic biology in engineering microbial communities for precision medicine.

Asiya Nazir, Fathima Hasnain Nadeem Hussain, Afsheen Raza.

  Over recent years, studies on microbiota research and synthetic biology have explored novel approaches microbial manipulation for therapeutic purposes. However, fragmented information is available on this aspect with key insights scattered across various disciplines such as molecular biology, genetics, bioengineering, and medicine. This review aims to the transformative potential of synthetic biology in advancing microbiome research and therapies, with significant implications for healthcare, agriculture, and environmental sustainability. By merging computer science, engineering, and biology, synthetic biology allows for precise design and modification of biological systems via cutting edge technologies like CRISPR/Cas9 gene editing, metabolic engineering, and synthetic oligonucleotide synthesis, thus paving the way for targeted treatments such as personalized probiotics and engineered microorganisms. The review will also highlight the vital role of gut microbiota in disorders caused by its dysbiosis and suggesting microbiota-based therapies and innovations such as biosensors for real-time gut health monitoring, non-invasive diagnostic tools, and automated bio foundries for better outcomes. Moreover, challenges including genetic stability, environmental safety, and robust regulatory frameworks will be discussed to understand the importance of ongoing research to ensure safe and effective microbiome interventions.

Keywords:  CRISPR/Cas9 gene editing; gut microbiota therapeutics; metabolic engineering; personalized medicine; synthetic biology

DOI:  https://doi.org/10.3389/fbioe.2024.1511149
Front Oncol. 2024 ;14 1506849

Crosstalk between lactate and tumor-associated immune cells: clinical relevance and insight.

Kemin Sun, Ye Shen, Xiang Xiao, Hao Xu, Quanli Zhang, Ming Li.

  Lactate, which was traditionally viewed as a metabolic byproduct of anaerobic glycolysis, has emerged as a significant signaling molecule involved in the development of tumors. Current studies highlight its dual function, where it not only fuels tumor development but also modulates immune responses. Lactate has an effect on various tumor-associated immune cells, promoting immunosuppressive conditions that facilitate tumor growth and immune evasion. This phenomenon is strongly associated with the Warburg effect, a metabolic shift observed in many cancers that favors glycolysis over oxidative phosphorylation, resulting in elevated lactate production. Exploring the complex interplay between lactate metabolism and tumor immunity provides a novel understanding regarding the mechanisms of tumor immune evasion and resistance to therapies. This review discusses the unique biology of lactate in the TME, its impact on immune cell dynamics, and its potential as a tumor treatment target.

Keywords:  Warburg effect; cancer immunotherapy; immunosuppression; lactate; tumor microenvironment

DOI:  https://doi.org/10.3389/fonc.2024.1506849
BMC Biotechnol. 2024 Dec 18. 24(1): 106

Targeting quorum sensing for manipulation of commensal microbiota.

Zachary Ziegert, Matthew Dietz, Max Hill, Marjais McBride, Elizabeth Painter, Mikael H Elias, Christopher Staley.

  Bacteria communicate through the accumulation of autoinducer (AI) molecules that regulate gene expression at critical densities in a process called quorum sensing (QS). Extensive work using simple systems and single strains of bacteria have revealed a role for QS in the regulation of virulence factors and biofilm formation; however, less is known about QS dynamics among communities, especially in vivo. In this review, we summarize the diversity of QS signals as well as their ability to influence "non-target" behaviors among species that have receptors but not synthases for those signals. We highlight host-microbe interactions facilitated by QS and describe cross-talk between QS and the mammalian endocrine and immune systems, as well as host surveillance of QS. Further, we describe emerging evidence for the role of QS in non-infectious, chronic, microbially associated diseases including inflammatory bowel diseases and cancers. Finally, we describe potential therapeutic approaches that involve leveraging QS signals as well as quorum quenching approaches to block signaling in vivo to mitigate deleterious consequences to the host. Ultimately, QS offers a previously underexplored target that may be leveraged for precision modification of the microbiota without deleterious bactericidal consequences.

Keywords:  Bacterial communication; Gut microbiota; Microbiota therapeutics; Quorum quenching; Quorum sensing; Signaling

DOI:  https://doi.org/10.1186/s12896-024-00937-3