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Frontiers in Immunology 2023The human gastrointestinal mucosa is colonized by thousands of microorganisms, which participate in a variety of physiological functions. Intestinal dysbiosis is closely... (Review)
Review
The human gastrointestinal mucosa is colonized by thousands of microorganisms, which participate in a variety of physiological functions. Intestinal dysbiosis is closely associated with the pathogenesis of several human diseases. Innate lymphoid cells (ILCs), which include NK cells, ILC1s, ILC2s, ILC3s and LTi cells, are a type of innate immune cells. They are enriched in the mucosal tissues of the body, and have recently received extensive attention. The gut microbiota and its metabolites play important roles in various intestinal mucosal diseases, such as inflammatory bowel disease (IBD), allergic disease, and cancer. Therefore, studies on ILCs and their interaction with the gut microbiota have great clinical significance owing to their potential for identifying pharmacotherapy targets for multiple related diseases. This review expounds on the progress in research on ILCs differentiation and development, the biological functions of the intestinal microbiota, and its interaction with ILCs in disease conditions in order to provide novel ideas for disease treatment in the future.
Topics: Humans; Gastrointestinal Microbiome; Immunity, Innate; Immunity, Mucosal; Intestinal Mucosa; Killer Cells, Natural
PubMed: 37304260
DOI: 10.3389/fimmu.2023.1171680 -
Inflammatory Bowel Diseases Feb 2004
Review
Topics: Crohn Disease; Humans; Immunity, Mucosal; Models, Immunological
PubMed: 15168827
DOI: 10.1097/00054725-200402001-00006 -
Journal of Experimental & Clinical... Jan 2021The stimulator of interferon genes (STING) connects microbial cytosolic sensing with host cell effector functions. STING signaling plays a central role in cyclic... (Review)
Review
The stimulator of interferon genes (STING) connects microbial cytosolic sensing with host cell effector functions. STING signaling plays a central role in cyclic dinucleotides (CDNs) and DNA sensing to induce secretion of interferons and pro-inflammatory mediators. Although activated STING signaling favors antimicrobial progress and facilitates mucosal would healing, its role in mucosal immunity and gut homeostasis is paradoxical, ranging from positive and negative effects within the gut. In our review, we summarize recent advance of STING signaling in gut homeostasis and inflammation, especially focusing on its molecular basis in mucosal immune response. Deep understanding of the regulatory mechanisms of intestinal STING pathway could promote clinical manipulation of this fundamental signaling as a promising immunomodulatory therapy.
Topics: Animals; Gastrointestinal Microbiome; Humans; Immunity, Mucosal; Inflammation; Interferons; Mice
PubMed: 33485379
DOI: 10.1186/s13046-021-01850-9 -
Life Sciences May 2024Gut microbiota is a complex microbial community with the ability of maintaining intestinal health. Intestinal homeostasis largely depends on the mucosal immune system to... (Review)
Review
Gut microbiota is a complex microbial community with the ability of maintaining intestinal health. Intestinal homeostasis largely depends on the mucosal immune system to defense external pathogens and promote tissue repair. In recent years, growing evidence revealed the importance of gut microbiota in shaping intestinal mucosal immunity. Therefore, according to the existing findings, this review first provided an overview of intestinal mucosal immune system before summarizing the regulatory roles of gut microbiota in intestinal innate and adaptive immunity. Specifically, this review delved into the gut microbial interactions with the cells such as intestinal epithelial cells (IECs), macrophages, dendritic cells (DCs), neutrophils, and innate lymphoid cells (ILCs) in innate immunity, and T and B lymphocytes in adaptive immunity. Furthermore, this review discussed the main effects of gut microbiota dysbiosis in intestinal diseases and offered future research prospects. The review highlighted the key regulatory roles of gut microbiota in intestinal mucosal immunity via various host-microbe interactions, providing valuable references for the development of microbial therapy in intestinal diseases.
Topics: Humans; Gastrointestinal Microbiome; Immunity, Innate; Immunity, Mucosal; Lymphocytes; Intestinal Mucosa; Macrophages; Intestinal Diseases
PubMed: 38588949
DOI: 10.1016/j.lfs.2024.122612 -
Terapevticheskii Arkhiv Apr 2018The outcome of diseases accompanied or caused by mucostasis depends both on the restoration of drainage function of the airways and on the effectiveness of immune... (Review)
Review
The outcome of diseases accompanied or caused by mucostasis depends both on the restoration of drainage function of the airways and on the effectiveness of immune mechanisms against pathogens. N-acetylcysteine (NAC) is widely used as mucolytic and antioxidant remedy in clinical practice. In this regard, the data of the scientific literature on the direct and indirect effects of NAC on the mucosal immunity of the respiratory tract have been reviewed. NAC possesses pleiotropic immunomodulating properties, most of which contribute to the regression of clinical manifestations of acute and chronic inflammatory diseases of the respiratory tract. Biological and pharmacological effects of NAC include improvement in rheological properties of mucus, reduction of excess mucin production, restoration of mucociliary clearance and production of sIgA, suppression of excess production of IgE and IgG4, destruction of biofilms and inhibition of their formation, suppression of adhesion of pathogenic bacteria to epithelial cells, antioxidant activity, regulation of the production of pro-inflammatory and profibrotic cytokines. There was no convincing evidence that NAC is able to suppress any component of mucosal immunity. For final conclusions on this subject, further research are required.
Topics: Acetylcysteine; Expectorants; Humans; Immunity, Mucosal; Mucociliary Clearance; Mucus
PubMed: 30701862
DOI: 10.26442/terarkh201890389-95 -
Nano Letters Nov 2023Intranasal vaccines can induce protective immune responses at the mucosa surface entrance, preventing the invasion of respiratory pathogens. However, the nasal barrier...
Intranasal vaccines can induce protective immune responses at the mucosa surface entrance, preventing the invasion of respiratory pathogens. However, the nasal barrier remains a major challenge in the development of intranasal vaccines. Herein, a transmucosal nanovaccine based on cationic fluorocarbon modified chitosan (FCS) is developed to induce mucosal immunity. In our system, FCS can self-assemble with the model antigen ovalbumin and TLR9 agonist CpG, effectively promoting the maturation and cross-presentation of dendritic cells. More importantly, it can enhance the production of secretory immunoglobin A (sIgA) at mucosal surfaces for those intranasally vaccinated mice, which in the meantime showed effective production of immunoglobulin G (IgG) systemically. As a proof-of-concept study, such a mucosal vaccine inhibits ovalbumin-expressing B16-OVA melanoma, especially its lung metastases. Our work presents a unique intranasal delivery system to deliver antigen across mucosal epithelia and promote mucosal and systemic immunity.
Topics: Mice; Animals; Ovalbumin; Immunity, Mucosal; Adjuvants, Immunologic; Antigens; Mucous Membrane; Vaccines; Mice, Inbred BALB C
PubMed: 37943583
DOI: 10.1021/acs.nanolett.3c03419 -
Trends in Immunology Feb 2020Secretory IgMs (SIgMs) were amongst the first identified immunoglobulins. However, their importance was not fully understood and recent advances have shown they play a... (Review)
Review
Secretory IgMs (SIgMs) were amongst the first identified immunoglobulins. However, their importance was not fully understood and recent advances have shown they play a key role in establishing and promoting commensal gut tolerance in mice and humans. The true interactions between SIgMs and the microbiota remain controversial and we aim to consolidate current knowledge in this review. Through comprehensive examination of SIgMs and their corresponding B cell secretors in several different pathological immunological contexts, we review the presumed role of these molecules in gut tolerance, inflammatory bowel diseases, and lung immunity. As SIgMs harbor a mostly tolerogenic function, we posit that their inclusion in further immunological research is paramount.
Topics: Humans; Immune Tolerance; Immunity, Mucosal; Immunoglobulin M; Inflammatory Bowel Diseases; Intestinal Mucosa; Microbiota
PubMed: 31928913
DOI: 10.1016/j.it.2019.12.005 -
American Journal of Respiratory Cell... Sep 2022
Topics: Immunity, Mucosal; Respiratory System
PubMed: 35704450
DOI: 10.1165/rcmb.2022-0210ED -
International Journal of Molecular... May 2022The gastrointestinal tract is the largest mucosal surface in our body and accommodates the majority of the total lymphocyte population. Being continuously exposed to... (Review)
Review
The gastrointestinal tract is the largest mucosal surface in our body and accommodates the majority of the total lymphocyte population. Being continuously exposed to both harmless antigens and potentially threatening pathogens, the intestinal mucosa requires the integration of multiple signals for balancing immune responses. This integration is certainly supported by tissue-resident intestinal mesenchymal cells (IMCs), yet the molecular mechanisms whereby IMCs contribute to these events remain largely undefined. Recent studies using single-cell profiling technologies indicated a previously unappreciated heterogeneity of IMCs and provided further knowledge which will help to understand dynamic interactions between IMCs and hematopoietic cells of the intestinal mucosa. In this review, we focus on recent findings on the immunological functions of IMCs: On one hand, we discuss the steady-state interactions of IMCs with epithelial cells and hematopoietic cells. On the other hand, we summarize our current knowledge about the contribution of IMCs to the development of intestinal inflammatory conditions, such as infections, inflammatory bowel disease, and fibrosis. By providing a comprehensive list of cytokines and chemokines produced by IMCs under homeostatic and inflammatory conditions, we highlight the significant immunomodulatory and tissue niche forming capacities of IMCs.
Topics: Homeostasis; Humans; Immunity, Mucosal; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Mesenchymal Stem Cells
PubMed: 35563571
DOI: 10.3390/ijms23095181 -
Wiley Interdisciplinary Reviews.... 2016The mucosal surfaces of the genital tract are the site of entry to over 30 different bacterial, parasitic, and viral pathogens that are the cause of sexually transmitted... (Review)
Review
The mucosal surfaces of the genital tract are the site of entry to over 30 different bacterial, parasitic, and viral pathogens that are the cause of sexually transmitted infections (STIs) including HIV. Women and adolescent girls are more severely impacted by STIs than men due in part to a greater biological susceptibility for acquiring infections and differences in disease sequelae. While it is widely accepted that preventative vaccines against the most commonly transmitted STIs would have a major impact on decreasing the global health burden of STIs for women worldwide, several challenges preclude their development. The female genital tract is a complex niche of microflora, hormonal influences, and immune tissues and cells that result in a mucosal immune system that is distinct from other mucosal sites and from our systemic immune system. An appreciation of these differences and their effect on shaping mucosal immunity to sexually transmitted pathogens is an important determinant for the design of effective STI vaccines. Here we describe the anatomy and mucosal immune system of the female reproductive tract, and discuss bioengineering strategies to design mucosal vaccines that overcome delivery challenges and coordinate the presentation kinetics and compartmentalization of antigens and adjuvants to relevant mucosal immune cell subsets. In particular, we describe recent progress in understanding the role of specific mucosal dendritic cell subsets in facilitating immune responses to pathogenic microbes in the genital mucosa. We also discuss the development of pathogen-mimicking materials that may be useful for engineering protective immunity in this mucosal niche.
Topics: Animals; Bioengineering; Female; Genitalia, Female; Humans; Immunity, Mucosal; Mice; Mucous Membrane; Sexually Transmitted Diseases
PubMed: 26153141
DOI: 10.1002/wnan.1359