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Nature Aug 2023The physiological functions of mast cells remain largely an enigma. In the context of barrier damage, mast cells are integrated in type 2 immunity and, together with...
The physiological functions of mast cells remain largely an enigma. In the context of barrier damage, mast cells are integrated in type 2 immunity and, together with immunoglobulin E (IgE), promote allergic diseases. Allergic symptoms may, however, facilitate expulsion of allergens, toxins and parasites and trigger future antigen avoidance. Here, we show that antigen-specific avoidance behaviour in inbred mice is critically dependent on mast cells; hence, we identify the immunological sensor cell linking antigen recognition to avoidance behaviour. Avoidance prevented antigen-driven adaptive, innate and mucosal immune activation and inflammation in the stomach and small intestine. Avoidance was IgE dependent, promoted by Th2 cytokines in the immunization phase and by IgE in the execution phase. Mucosal mast cells lining the stomach and small intestine rapidly sensed antigen ingestion. We interrogated potential signalling routes between mast cells and the brain using mutant mice, pharmacological inhibition, neural activity recordings and vagotomy. Inhibition of leukotriene synthesis impaired avoidance, but overall no single pathway interruption completely abrogated avoidance, indicating complex regulation. Collectively, the stage for antigen avoidance is set when adaptive immunity equips mast cells with IgE as a telltale of past immune responses. On subsequent antigen ingestion, mast cells signal termination of antigen intake. Prevention of immunopathology-causing, continuous and futile responses against per se innocuous antigens or of repeated ingestion of toxins through mast-cell-mediated antigen-avoidance behaviour may be an important arm of immunity.
Topics: Animals; Mice; Allergens; Avoidance Learning; Hypersensitivity; Immunoglobulin E; Mast Cells; Stomach; Vagotomy; Immunity, Innate; Immunity, Mucosal; Th2 Cells; Cytokines; Leukotrienes; Intestine, Small
PubMed: 37438525
DOI: 10.1038/s41586-023-06188-0 -
Nature Immunology Sep 2023Omnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time, but the...
Omnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time, but the health consequences of this short-term consumption of energy-dense nutrients are unclear. Here, we show that short-term reiterative switching to 'feast diets', mimicking our social eating behavior, breaches the potential buffering effect of the intestinal microbiota and reorganizes the immunological architecture of mucosa-associated lymphoid tissues. The first dietary switch was sufficient to induce transient mucosal immune depression and suppress systemic immunity, leading to higher susceptibility to Salmonella enterica serovar Typhimurium and Listeria monocytogenes infections. The ability to respond to antigenic challenges with a model antigen was also impaired. These observations could be explained by a reduction of CD4 T cell metabolic fitness and cytokine production due to impaired mTOR activity in response to reduced microbial provision of fiber metabolites. Reintroducing dietary fiber rewired T cell metabolism and restored mucosal and systemic CD4 T cell functions and immunity. Finally, dietary intervention with human volunteers confirmed the effect of short-term dietary switches on human CD4 T cell functionality. Therefore, short-term nutritional changes cause a transient depression of mucosal and systemic immunity, creating a window of opportunity for pathogenic infection.
Topics: Humans; Mice; Animals; Mucous Membrane; Salmonella typhimurium; T-Lymphocytes; Immunity, Mucosal
PubMed: 37580603
DOI: 10.1038/s41590-023-01587-x -
Clinical Microbiology Reviews Sep 2023and belong to the genus , which comprises 14 other species. is responsible for whooping cough in humans, a severe infection in children and less severe or chronic in... (Review)
Review
and belong to the genus , which comprises 14 other species. is responsible for whooping cough in humans, a severe infection in children and less severe or chronic in adults. These infections are restricted to humans and currently increasing worldwide. is involved in diverse respiratory infections in a wide range of mammals. For instance, the canine infectious respiratory disease complex (CIRDC), characterized by a chronic cough in dogs. At the same time, it is increasingly implicated in human infections, while remaining an important pathogen in the veterinary field. Both can evade and modulate host immune responses to support their persistence, although it is more pronounced in infection. The protective immune responses elicited by both pathogens are comparable, while there are important characteristics in the mechanisms that differ. However, pathogenesis is more difficult to decipher in animal models than those of because of its restriction to humans. Nevertheless, the licensed vaccines for each are different in terms of formulation, route of administration and immune responses induced, with no known cross-reaction between them. Moreover, the target of the mucosal tissues and the induction of long-lasting cellular and humoral responses are required to control and eliminate . In addition, the interaction between both veterinary and human fields are essential for the control of this genus, by preventing the infections in animals and the subsequent zoonotic transmission to humans.
Topics: Child; Animals; Dogs; Humans; Bordetella pertussis; Bordetella bronchiseptica; Whooping Cough; Bordetella Infections; Respiratory Tract Infections; Vaccines; Mammals
PubMed: 37306571
DOI: 10.1128/cmr.00164-22 -
Emerging Microbes & Infections Dec 2023African swine fever (ASF) is an acute and highly contagious lethal infectious disease in swine that severely threatens the global pig industry. At present, a safe and...
African swine fever (ASF) is an acute and highly contagious lethal infectious disease in swine that severely threatens the global pig industry. At present, a safe and efficacious vaccine is urgently required to prevent and control the disease. In this study, we evaluated the safety and immunogenicity of replication-incompetent type-2 adenoviruses carrying African swine fever virus (ASFV) antigens, namely (p30), (p54), (CD2v), (p72), and (p72 chaperone). A vaccine cocktail delivered by simultaneous intramuscular (IM) and intranasal (IN) administration robustly elicited both systemic and mucosal immune responses against AFSV in mice and swine and provided highly effective protection against the circulating ASFV strain in farmed pigs. This multi-antigen cocktail vaccine was well tolerated in the vaccinated animals. No significant interference among antigens was observed. The combined IM and IN vaccination using this adenovirus-vectored antigen cocktail vaccine warrants further evaluation for providing safe and effective protection against ASFV infection and transmission.
Topics: Swine; Animals; Mice; African Swine Fever Virus; African Swine Fever; Adenoviridae; Adenovirus Vaccines; Antigens, Viral; Viral Vaccines; Adenoviridae Infections; Vaccination
PubMed: 37401832
DOI: 10.1080/22221751.2023.2233643 -
Frontiers in Endocrinology 2023Inflammatory bowel disease (IBD) is a chronic, relapsing gastrointestinal (GI) disorder characterized by intestinal inflammation. The etiology of IBD is multifactorial... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic, relapsing gastrointestinal (GI) disorder characterized by intestinal inflammation. The etiology of IBD is multifactorial and results from a complex interplay between mucosal immunity, environmental factors, and host genetics. Future therapeutics for GI disorders, including IBD, that are driven by oxidative stress require a greater understanding of the cellular and molecular mechanisms mediated by reactive oxygen species (ROS). In the GI tract, oxidative stressors include infections and pro-inflammatory responses, which boost ROS generation by promoting the production of pro-inflammatory cytokines. Nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) represent two important signaling pathways in intestinal immune cells that regulate numerous physiological processes, including anti-inflammatory and antioxidant activities. Natural antioxidant compounds exhibit ROS scavenging and increase antioxidant defense capacity to inhibit pro-oxidative enzymes, which may be useful in IBD treatment. In this review, we discuss various polyphenolic substances (such as resveratrol, curcumin, quercetin, green tea flavonoids, caffeic acid phenethyl ester, luteolin, xanthohumol, genistein, alpinetin, proanthocyanidins, anthocyanins, silymarin), phenolic compounds including thymol, alkaloids such as berberine, storage polysaccharides such as tamarind xyloglucan, and other phytochemicals represented by isothiocyanate sulforaphane and food/spices (such as ginger, flaxseed oil), as well as antioxidant hormones like melatonin that target cellular signaling pathways to reduce intestinal inflammation occurring with IBD.
Topics: Humans; Antioxidants; Reactive Oxygen Species; Anthocyanins; Oxidative Stress; Inflammatory Bowel Diseases; Hormones; Inflammation
PubMed: 37701897
DOI: 10.3389/fendo.2023.1217165 -
The Veterinary Quarterly Dec 2023Influenza A virus is a negative-sense single-stranded RNA virus that belongs to Orthomyxoviridae family. Based on the antigenic characteristics of hemagglutinin (HA) and... (Review)
Review
Influenza A virus is a negative-sense single-stranded RNA virus that belongs to Orthomyxoviridae family. Based on the antigenic characteristics of hemagglutinin (HA) and neuraminidase (NA) influenza viruses are classified into multiple subtypes. H9N2 belongs to the low pathogenic Avian Influenza Viruses (AIVs) and is one of the widely spread viruses in poultry, which can pose a threat to humans by directly infecting or providing internal genes for various zoonotic avian influenza strains. It has the potential to directly or indirectly participate in becoming an AIV that causes a human pandemic. When the virus enters a host, the innate immune system is activated first by pattern recognition receptors. The cytokines produced at the site of infection recruit innate immune cells and antigen-presenting cells and those cells subsequently transmit antigenic signals to adaptive immune cells (i.e. B cells and T cells), to trigger specific humoral and cellular immune responses. As a result, humoral and cellular immunity can clear virus and infected cells antibody-mediated neutralization and cytotoxicity, respectively. Understanding how chicken immune systems respond to H9N2 is a top priority for effectively controlling the virus's spread and designing vaccines. In this review, we comprehensively discuss the role of the chicken immune system in defending against H9N2, and clarify the current limitations in understanding chicken immune responses to H9N2 virus, thereby providing potential directions for future research as research on the chicken respiratory mucosal immune system has been stagnant for more than 20 years especially on how the mucosal immune system in chicken responds to avian influenza.
Topics: Animals; Humans; Chickens; Influenza in Birds; Influenza A Virus, H9N2 Subtype; Poultry; Immune System
PubMed: 37357919
DOI: 10.1080/01652176.2023.2228360 -
Nature Reviews. Immunology Mar 2024MHC antigen presentation plays a fundamental role in adaptive and semi-invariant T cell immunity. Distinct MHC molecules bind antigens that differ in chemical structure,... (Review)
Review
MHC antigen presentation plays a fundamental role in adaptive and semi-invariant T cell immunity. Distinct MHC molecules bind antigens that differ in chemical structure, origin and location and present them to specialized T cells. MHC class I-related protein 1 (MR1) presents a range of small molecule antigens to MR1-restricted T (MR1T) lymphocytes. The best studied MR1 ligands are derived from microbial metabolism and are recognized by a major class of MR1T cells known as mucosal-associated invariant T (MAIT) cells. Here, we describe the MR1 antigen presentation pathway: the known types of antigens presented by MR1, the location where MR1-antigen complexes form, the route followed by the complexes to the cell surface, the mechanisms involved in termination of MR1 antigen presentation and the accessory cellular proteins that comprise the MR1 antigen presentation machinery. The current road map of the MR1 antigen presentation pathway reveals potential strategies for therapeutic manipulation of MR1T cell function and provides a foundation for further studies that will lead to a deeper understanding of MR1-mediated immunity.
Topics: Humans; Antigen Presentation; Mucosal-Associated Invariant T Cells; Minor Histocompatibility Antigens; Histocompatibility Antigens Class I; Antigens
PubMed: 37773272
DOI: 10.1038/s41577-023-00934-1 -
Frontiers in Immunology 2023
Topics: Humans; Female; Immunity, Mucosal; Bacterial Proteins
PubMed: 37854596
DOI: 10.3389/fimmu.2023.1282709 -
European Journal of Medical Research Aug 2023Secretory immunoglobulin A (SIgA) is one of the most abundant immunoglobulin subtypes among mucosa, which plays an indispensable role in the first-line protection... (Review)
Review
Secretory immunoglobulin A (SIgA) is one of the most abundant immunoglobulin subtypes among mucosa, which plays an indispensable role in the first-line protection against invading pathogens and antigens. Therefore, the role of respiratory SIgA in respiratory mucosal immune diseases has attracted more and more attention. Although the role of SIgA in intestinal mucosal immunity has been widely studied, the cell types responsible for SIgA and the interactions between cells are still unclear. Here, we conducted a wide search of relevant studies and sorted out the relationship between SIgA and some pulmonary diseases (COPD, asthma, tuberculosis, idiopathic pulmonary fibrosis, COVID-19, lung cancer), which found SIgA is involved in the pathogenesis and progression of various lung diseases, intending to provide new ideas for the prevention, diagnosis, and treatment of related lung diseases.
Topics: Humans; Immunoglobulin A, Secretory; COVID-19; Lung Neoplasms; Cell Movement; Idiopathic Pulmonary Fibrosis
PubMed: 37635240
DOI: 10.1186/s40001-023-01282-5 -
Current Opinion in Immunology Oct 2023Delivery of vaccines via the mucosal route is regarded as the most effective mode of immunization to counteract infectious diseases that enter via mucosal tissues,... (Review)
Review
Delivery of vaccines via the mucosal route is regarded as the most effective mode of immunization to counteract infectious diseases that enter via mucosal tissues, including oral, nasal, pulmonary, intestinal, and urogenital surfaces. Mucosal vaccines not only induce local immune effector elements, such as secretory Immunoglobulin A (IgA) reaching the luminal site of the mucosa, but also systemic immunity. Moreover, mucosal vaccines may trigger immunity in distant mucosal tissues because of the homing of primed antigen-specific immune cells toward local and distant mucosal tissue via the common mucosal immune system. While most licensed intramuscular vaccines induce only systemic immunity, next-generation mucosal vaccines may outperform parenteral vaccination strategies by also eliciting protective mucosal immune responses that block infection and/or transmission. Especially the nasal route of vaccination, targeting the nasal-associated lymphoid tissue, is attractive for local and distant mucosal immunization. In numerous studies, bacterial outer membrane vesicles (OMVs) have proved attractive as vaccine platform for homologous bacterial strains, but also as antigen delivery platform for heterologous antigens of nonbacterial diseases, including viruses, parasites, and cancer. Their application has also been extended to mucosal delivery. Here, we will summarize the characteristics and clinical potential of (engineered) OMVs as vaccine platform for mucosal, especially intranasal delivery.
Topics: Humans; Vaccines; Administration, Intranasal; Immunization; Vaccination; Immunity, Mucosal; Mucous Membrane
PubMed: 37598549
DOI: 10.1016/j.coi.2023.102376