bims-bac4me Biomed News
on Microbiome and trained immunity
Issue of 2023‒02‒26
fourteen papers selected by
Chun-Chi Chang
University Hospital Zurich

  1. Nat Immunol. 2023 Feb 20.
      Respiratory viral infections reprogram pulmonary macrophages with altered anti-infectious functions. However, the potential function of virus-trained macrophages in antitumor immunity in the lung, a preferential target of both primary and metastatic malignancies, is not well understood. Using mouse models of influenza and lung metastatic tumors, we show here that influenza trains respiratory mucosal-resident alveolar macrophages (AMs) to exert long-lasting and tissue-specific antitumor immunity. Trained AMs infiltrate tumor lesions and have enhanced phagocytic and tumor cell cytotoxic functions, which are associated with epigenetic, transcriptional and metabolic resistance to tumor-induced immune suppression. Generation of antitumor trained immunity in AMs is dependent on interferon-γ and natural killer cells. Notably, human AMs with trained immunity traits in non-small cell lung cancer tissue are associated with a favorable immune microenvironment. These data reveal a function for trained resident macrophages in pulmonary mucosal antitumor immune surveillance. Induction of trained immunity in tissue-resident macrophages might thereby be a potential antitumor strategy.
  2. J Leukoc Biol. 2023 Feb 01. 113(2): 164-190
      Several studies over the last decade have identified intimate links between cellular metabolism and macrophage function. Metabolism has been shown to both drive and regulate macrophage function by producing bioenergetic and biosynthetic precursors as well as metabolites (and other bioactive molecules) that regulate gene expression and signal transduction. Many studies have focused on lipopolysaccharide-induced reprogramming, assuming that it is representative of most inflammatory responses. However, emerging evidence suggests that diverse pathogen-associated molecular patterns (PAMPs) are associated with unique metabolic profiles, which may drive pathogen specific immune responses. Further, these metabolic pathways and processes may act as a rheostat to regulate the magnitude of an inflammatory response based on the biochemical features of the local microenvironment. In this review, we will discuss recent work examining the relationship between cellular metabolism and macrophage responses to viral PAMPs and describe how these processes differ from lipopolysaccharide-associated responses. We will also discuss how an improved understanding of the specificity of these processes may offer new insights to fine-tune macrophage function during viral infections or when using viral PAMPs as therapeutics.
    Keywords:  antiviral responses; immunometabolism; macrophage; mitochondria; pathogen-associated molecular patterns; pattern recognition receptors
  3. J Leukoc Biol. 2023 Jan 20. pii: qiad003. [Epub ahead of print]
      Polyvalent mechanical bacterial lysate is effective in the prevention of respiratory tract infections, although its mechanism of action is not entirely elucidated. Because epithelial cells constitute the frontline defense against infections, we investigated the molecular mechanisms of innate response exerted by bronchial epithelial cells in the presence of polyvalent mechanical bacterial lysate. By using primary human bronchial epithelial cells, we observed that polyvalent mechanical bacterial lysate was able to increase the expression of cellular adhesion molecules such as ICAM-1 and E-cadherin, as well as the expression of amphiregulin, a growth factor able to support human bronchial epithelial cell proliferation. Remarkably, polyvalent mechanical bacterial lysate promoted in human bronchial epithelial cells the de novo expression of human β-defensin-2, a major antimicrobial peptide, conferring them a direct antimicrobial activity. Moreover, polyvalent mechanical bacterial lysate-stimulated human bronchial epithelial cells provided signals for increased IL-22 production by innate lymphoid cells via IL-23, which could further contribute to the release of antimicrobial peptides by epithelial cells. In agreement with these in vitro data, the concentration of both IL-23 and antimicrobial peptides (human β-defensin-2 and LL-37) increased in the saliva of healthy volunteers after sublingual administration of polyvalent mechanical bacterial lysate. Altogether, these results indicate that polyvalent mechanical bacterial lysate administration might support mucosal barrier integrity and promote mechanisms of antimicrobial activity in airway epithelial cells.
    Keywords:  antimicrobial peptides; bacterial lysate; dendritic cells; epithelial cells; innate lymphoid cells; saliva samples
  4. Pneumonia (Nathan). 2023 Feb 25. 15(1): 4
      The lungs are an immunologically unique environment; they are exposed to innumerable pathogens and particulate matter daily. Appropriate clearance of pathogens and response to pollutants is required to prevent overwhelming infection, while preventing tissue damage and maintaining efficient gas exchange. Broadly, the innate immune system is the collection of immediate, intrinsic immune responses to pathogen or tissue injury. In this review, we will examine the innate immune responses of the lung, with a particular focus on their role in pneumonia. We will discuss the anatomic barriers and antimicrobial proteins of the lung, pathogen and injury recognition, and the role of leukocytes (macrophages, neutrophils, and innate lymphocytes) and lung stromal cells in innate immunity. Throughout the review, we will focus on new findings in innate immunity as well as features that are unique to the lung.
    Keywords:  Bacterial pneumonia; Extracellular matrix; Innate immunity; Innate lymphocytes; Lung endothelium; Lung epithelium; Macrophage; Neutrophil; Viral pneumonia
  5. Expert Rev Clin Immunol. 2023 Feb 21.
      INTRODUCTION: Innate immunity serves as the frontline to combat invading pathogens. Oral microbiota is the total collection of microorganisms colonized within the oral cavity. By recognizing the resident microorganisms through pattern recognition receptors, innate immunity is capable of interacting with oral microbiota and maintaining homeostasis. Dysregulation of interaction may lead to the pathogenesis of several oral diseases. Decoding the crosstalk between oral microbiota and innate immunity may be contributory to developing novel therapies for preventing and treating oral diseases.AREAS COVERED: This article reviewed pattern recognition receptors in the recognition of oral microbiota, the reciprocal interaction between innate immunity and oral microbiota, and discussed how the dysregulation of this relationship lead to the pathogenesis and development of oral diseases.
    EXPERT OPINION: Many studies have been conducted to illustrate the relationship between oral microbiota and innate immunity and its role in the occurrence of different oral diseases. The impact and mechanisms of innate immune cells on oral microbiota and the mechanisms of dysbiotic microbiota in altering innate immunity are still needed to be investigated. Altering the oral microbiota might be a possible solution for treating and preventing oral diseases.
    Keywords:  apical periodontitis; dendritic cell; innate immunity; macrophage; neutrophil; oral cancer; oral microbiota; periodontitis; pulpitis
  6. Trends Microbiol. 2023 Feb 21. pii: S0966-842X(23)00027-6. [Epub ahead of print]
      The corneocyte layers forming the upper surface of mammalian skin are embedded in a lamellar-membrane matrix which repels harmful molecules while retaining solutes from subcutaneous tissues. Only certain bacterial and fungal taxa colonize skin surfaces. They have ways to use epidermal lipids as nutrients while resisting antimicrobial fatty acids. Skin microorganisms release lipophilic microbe-associated molecular pattern (MAMP) molecules which are largely retained by the epidermal lipid barrier. Skin barrier defects, as in atopic dermatitis, impair lamellar-membrane integrity, resulting in altered skin microbiomes, which then include the pathogen Staphylococcus aureus. The resulting increased penetration of MAMPs and toxins promotes skin inflammation. Elucidating how microorganisms manipulate the epidermal lipid barrier will be key for better ways of preventing inflammatory skin disorders.
    Keywords:  antimicrobial lipids; atopic dermatitis; human skin microbiome; innate immunity; keratinocytes; lipolytic enzymes
  7. Res Sq. 2023 Feb 17. pii: [Epub ahead of print]
      Venous leg ulcers (VLU) are the most common chronic wounds characterized by bacterial biofilms and perturbed microbiome. Staphylococcus epidermidis is primarily known as skin commensal beneficial for the host, however, some strains can form biofilms and cause infections. By employing shotgun metagenomic sequencing we show that genetic signatures of antimicrobial resistance, adhesion and biofilm formation in VLU isolates correlate with in vitro bacterial traits. We demonstrate that the capability of chronic wound isolates to form biofilms and elicit IL-8 and IL-1β expression in human ex vivo wounds, correlates with the non-healing outcomes in patients with VLU. In contrast, commensal strains were incapable of surviving in the human ex vivo wounds. We show that major fitness traits of S. epidermis from VLU involve genes for resistance to methicillin and mupirocin, while the biofilm formation relied on the minimal number of genetic elements responsible for bacterial binding to fibronectin and fibrinogen. This underscores the importance of the emergence of treatment resistant virulent lineages in patients with non-healing wounds.
  8. Biochem Soc Trans. 2023 Feb 23. pii: BST20220014. [Epub ahead of print]
      Mitochondria have long been appreciated as the metabolic hub of cells. Emerging evidence also posits these organelles as hubs for innate immune signalling and activation, particularly in macrophages. Macrophages are front-line cellular defenders against endogenous and exogenous threats in mammals. These cells use an array of receptors and downstream signalling molecules to respond to a diverse range of stimuli, with mitochondrial biology implicated in many of these responses. Mitochondria have the capacity to both divide through mitochondrial fission and coalesce through mitochondrial fusion. Mitochondrial dynamics, the balance between fission and fusion, regulate many cellular functions, including innate immune pathways in macrophages. In these cells, mitochondrial fission has primarily been associated with pro-inflammatory responses and metabolic adaptation, so can be considered as a combative strategy utilised by immune cells. In contrast, mitochondrial fusion has a more protective role in limiting cell death under conditions of nutrient starvation. Hence, fusion can be viewed as a cellular survival strategy. Here we broadly review the role of mitochondria in macrophage functions, with a focus on how regulated mitochondrial dynamics control different functional responses in these cells.
    Keywords:  inflammation; macrophages; mitochondrial dynamics; mitochondrial fission; mitochondrial fusion; neuroinflammation
  9. Antibiotics (Basel). 2023 Feb 17. pii: 406. [Epub ahead of print]12(2):
      The ability of Staphylococcus aureus to colonise different niches across the human body is linked to an adaptable metabolic capability, as well as its ability to persist within specific tissues despite adverse conditions. In many cases, as S. aureus proliferates within an anatomical niche, there is an associated pathology. The immune response, together with medical interventions such as antibiotics, often removes the S. aureus cells that are causing this disease. However, a common issue in S. aureus infections is a relapse of disease. Within infected tissue, S. aureus exists as a population of cells, and it adopts a diversity of cell types. In evolutionary biology, the concept of "bet-hedging" has established that even in positive conditions, there are members that arise within a population that would be present as non-beneficial, but if those conditions change, these traits could allow survival. For S. aureus, some of these cells within an infection have a reduced fitness, are not rapidly proliferating or are the cause of an active host response and disease, but these do remain even after the disease seems to have been cleared. This is true for persistence against immune responses but also as a continual presence in spite of antibiotic treatment. We propose that the constant arousal of suboptimal populations at any timepoint is a key strategy for S. aureus long-term infection and survival. Thus, understanding the molecular basis for this feature could be instrumental to combat persistent infections.
    Keywords:  Staphylococcus aureus; persister cells; small colony variant (SCV)
  10. Mol Oral Microbiol. 2023 Feb 22.
      The onset and development of periodontitis centers around microbiota dysbiosis and disrupted host responses. Dynamic metabolic activities of the subgingival microbiota modify the polymicrobial community, shape the microenvironment, and modulate the host response. A complicated metabolic network exists in interspecies interactions between periodontal pathobionts and commensals, which can lead to the development of dysbiotic plaque. Dysbiotic subgingival microbiota undergo metabolic interactions with the host and disrupt host-microbe equilibrium. In this review, we discuss the metabolic profiles of the subgingival microbiota, the metabolic crosstalk in polymicrobial communities, including pathobionts and commensals, and the metabolic interactions between microbes and the host. This article is protected by copyright. All rights reserved.
    Keywords:  host-microbe interaction; metabolism; microbiota dysbiosis; subgingival microbiota
  11. J Infect Dis. 2023 Feb 20. pii: jiad046. [Epub ahead of print]
      Staphylococcus aureus (S. aureus) causes a broad range of infections. TLR2 senses the S. aureus lipoproteins in S. aureus infections. Aging raises the risk of infection. Our aim was to understand how aging and TLR2 impact the clinical outcomes of S. aureus bacteremia. Four groups of mice (Wild type/young, Wild type/old, TLR2-/-/young, and TLR2-/-/old) were intravenously infected with S. aureus, and the infection course was followed. Both TLR2 deficiency and aging enhanced the susceptibility to disease. Increased age was the main contributing factor to mortality and changes in spleen weight, whereas other clinical parameters such as weight loss and kidney abscess formation were more TLR2 dependent. Importantly, aging increased mortality without relying on TLR2. In vitro, both aging and TLR2 deficiency downregulated cytokine/chemokine production of immune cells with distinct patterns. In summary, we demonstrate that aging and TLR2 deficiency impair the immune response to S. aureus bacteremia in distinct ways.
    Keywords:   Staphylococcus aureus ; TLR2; aging; bacteremia; mouse
  12. Eur J Immunol. 2023 Feb 22. e2149499
      The skin and the oral mucosa represent interfaces to the environment that are constantly exposed to pathogens and harmless foreign antigens such as commensal bacteria. Both barrier organs share the presence of Langerhans cells (LC), distinctive members of the heterogeneous family of antigen-presenting dendritic cells (DC) that have the unique ability to promote tolerogenic as well as inflammatory immune responses. While skin LC have been extensively studied in the past decades, less is known about the function of oral mucosal LC. Despite similar transcriptomic signatures, skin and oral mucosal LC differ greatly in their ontogeny and development. In this review article, we will summarize the current knowledge on LC subsets in the skin compared to the oral mucosa. We will discuss the similarities and differences in their development, homeostasis and function in the two barrier tissues, including their interaction with the local microbiota. In addition, this review will update recent advances on the role of LC in inflammatory skin and oral mucosal diseases. This article is protected by copyright. All rights reserved.
    Keywords:  Langerhans cells; immune regulation; ontogeny; oral epithelium; skin epidermis
  13. Front Microbiol. 2023 ;14 1115556
      Cancer and microbial infections are significant worldwide health challenges. Numerous studies have demonstrated that bacteria may contribute to the emergence of cancer. In this review, we assemble bacterial species discovered in various cancers to describe their variety and specificity. The relationship between bacteria and macrophages in cancer is also highlighted, and we look for ample proof to establish a biological basis for bacterial-induced macrophage polarization. Finally, we quickly go over the potential roles of metabolites, cytokines, and microRNAs in the regulation of the tumor microenvironment by bacterially activated macrophages. The complexity of bacteria and macrophages in cancer will be revealed as we gain a better understanding of their pathogenic mechanisms, which will lead to new therapeutic approaches for both inflammatory illnesses and cancer.
    Keywords:  M1/M2 macrophage polarization; bacteria; cancer; tumor microenvironment; tumor-associated macrophages
  14. Adv Sci (Weinh). 2023 Feb 24. e2205473
      The oral cavity contains distinct microenvironments that serve as oral barriers, such as the non-shedding surface of the teeth (e.g., enamel), the epithelial mucosa and gingival tissue (attached gingiva) where microbial communities coexist. The interactions and balances between these communities are responsible for oral tissue homeostasis or dysbiosis, that ultimately dictate health or disease. Disruption of this equilibrium can lead to chronic inflammation and permanent tissue damage in the case of chronic periodontitis. There are currently no experimental tissue models able to mimic the structural, physical, and metabolic conditions present in the human oral gingival tissue to support the long-term investigation of host-pathogens imbalances. Herein, the authors report an in vitro 3D anatomical gingival tissue model, fabricated from silk biopolymer by casting a replica mold of an adult human mandibular gingiva to recreate a tooth-gum unit. The model is based on human primary cultures that recapitulate physiological tissue organization, as well as a native oxygen gradient within the gingival pocket to support human subgingival plaque microbiome with a physiologically relevant level of microbial diversity up to 24 h. The modulation of inflammatory markers in the presence of oral microbiome indicates the humanized functional response of this model and establishes a new set of tools to investigate host-pathogen imbalances in gingivitis and periodontal diseases.
    Keywords:  host-pathogen interactions; microbiome; nanomanufacturing; silk; tissue model