Development of Mucosal Immunity: Functional Interactions with Mucosal Microbiome in Health and Disease

2019 ◽  
Vol 15 (2) ◽  
pp. 154-165
Author(s):  
Oscar G. Gómez-Duarte ◽  
Pearay L. Ogra
Keyword(s):  
Adaptive Immunity ◽  
Mucosal Immunity ◽  
Plasma Cells ◽  
External Environment ◽  
Mammalian Host ◽  
Immune Functions ◽  
Principal Mechanism ◽  
Functional Development ◽  
Mucosal Surfaces ◽  
Specific Pathogen

The mucosal surfaces and the skin are the primary sites of interactions between the mammalian host and the external environment. These sites are exposed continuously to the diverse components of the environment, including subcellular, unicellular and multicellular organisms, dietary agents and food products; and numerous other soluble or cellular air or water borne products. The development of innate and adaptive immunity in the mucosal surfaces and the skin are the principal mechanism of mammalian defense evolved to date, in order to maintain effective homeostatic balance between the host and the external environment. The innate immune functions are mediated by a number of host specific Pathogen Recognition Receptors (PRR), designed to recognize unique Pathogen Associated Molecular Patterns (PAMP), essential to the molecular structure of the microorganism. The major components of specific adaptive immunity in the mucosal surfaces include the organized antigen-reactive lymphoid follicles in different inductive mucosal sites and the effector sites of the lamina propria and sub-epithelial regions, which contain lymphoid and plasma cells, derived by the homing of antigen sensitized cells from the inductive sites. The acquisition of environmental microbiome by the neonate in its mucosal surfaces and the skin, which begins before or immediately after birth, has been shown to play a critical and complex role in the development of mucosal immunity. This report provides an overview of the mammalian microbiome and highlights its role in the evolution and functional development of immunologic defenses in the mucosal surface under normal physiologic conditions and during infectious and non-infectious inflammatory pathologic states associated with altered microbiota.

scholarly journals Effect of Peptides from Alaska Pollock on Intestinal Mucosal Immunity Function and Purification of Active Fragments

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2517
Author(s):  
Qiqi Li ◽  
Shikai Wang ◽  
Supanooch Poungchawanwong ◽  
Hu Hou
Keyword(s):  
Body Weight ◽  
Mucosal Immunity ◽  
Plasma Cells ◽  
Intestinal Barrier ◽  
Mucosal Barrier ◽  
Immune Functions ◽  
Immune Organ ◽  
Intestinal Mucosal Barrier ◽  
Active Fragments ◽  
Immunity Function

The intestinal mucosal barrier plays an important role in systemic immune functions. This study aimed to find the mechanism of peptide from Alaska Pollock (APP) on intestinal mucosal immunity in mice induced by cyclophosphamide (Cy). Cy-induced decreases of body weight and index of immune organ were significantly improved by APP as compared with Cy group (p < 0.05). APP could promote the secretion of SIgA and IgA on intestinal mucosa (p < 0.05) and mainly had an impact on the final differentiation of IgA+ B cell, thereby promoting the secretion of plasma cells, which can be corroborated by the increases of IL-6 and IL-10 (p < 0.05). APP with high immune activity was separated and two peptides were purified and identified as Gly–Val–Ile–Lys and Ala–Cys–Asn–Gly–Arg. Therefore, APP can be considered as beneficial ingredients to protect the intestinal barrier disruption induced by Cy.

Immunity at Mucosal Surfaces

1996 ◽  
Vol 10 (1) ◽  
pp. 62-65 ◽  
Author(s):  
T.A. Brown
Keyword(s):  
Immune System ◽  
Mucosal Immunity ◽  
External Environment ◽  
Mucosal Immune System ◽  
Opportunistic Pathogens ◽  
Extrinsic Factors ◽  
Specific Immunity ◽  
Mucosal Surfaces

The mucosae form a barrier between our bodies and a hostile external environment. Diseases and extrinsic factors which impair mucosal function may lead to serious consequences. The mucosal immune system is the primary mediator of specific immunity at mucosal surfaces. As such, it is responsible for maintaining homeostasis and for defense against both overt and opportunistic pathogens. For this reason, it is also the target of many new vaccine strategies for the induction of mucosal immunity. This brief review will examine the mucosal immune system, its role in maintaining the integrity of the mucosa, and some of the strategies aimed at enhancing specific immunity.

scholarly journals Iron-Responsive Repression of Urease Expression in Helicobacter hepaticus Is Mediated by the Transcriptional Regulator Fur

2006 ◽  
Vol 75 (2) ◽  
pp. 745-752 ◽  
Author(s):  
Clara Belzer ◽  
Bart A. M. van Schendel ◽  
Ernst J. Kuipers ◽  
Johannes G. Kusters ◽  
Arnoud H. M. van Vliet
Keyword(s):  
Urease Activity ◽  
Transcriptional Regulator ◽  
Mammalian Host ◽  
Transcriptional Level ◽  
Helicobacter Hepaticus ◽  
Mucosal Surfaces ◽  
Insertional Inactivation ◽  
Fur Protein ◽  
Colonization Factors ◽  
Gene Recombinant

ABSTRACT Persistent colonization of mucosal surfaces by bacteria in the mammalian host requires concerted expression of colonization factors, depending on the environmental conditions. Helicobacter hepaticus is a urease-positive pathogen that colonizes the intestinal and hepatobiliary tracts of rodents. Here it is reported that urease expression of H. hepaticus is iron repressed by the transcriptional regulator Fur. Iron restriction of growth medium resulted in a doubling of urease activity in wild-type H. hepaticus strain ATCC 51449 and was accompanied by increased levels of urease subunit proteins and ureA mRNA. Insertional inactivation of the fur gene abolished iron-responsive repression of urease activity, whereas inactivation of the perR gene did not affect iron-responsive regulation of urease activity. The iron-responsive promoter element was identified directly upstream of the H. hepaticus ureA gene. Recombinant H. hepaticus Fur protein bound to this ureA promoter region in a metal-dependent matter, and binding resulted in the protection of a 41-bp, Fur box-containing operator sequence located at positions −35 to −75 upstream of the transcription start site. In conclusion, H. hepaticus Fur controls urease expression at the transcriptional level in response to iron availability. This represents a novel type of urease regulation in ureolytic bacteria and extends the already diverse regulatory repertoire of the Fur protein.

scholarly journals Correlations between Antibody Immune Responses at Different Mucosal Effector Sites Are Controlled by Antigen Type and Dosage

2000 ◽  
Vol 68 (7) ◽  
pp. 3830-3839 ◽  
Author(s):  
Dörthe Externest ◽  
Barbara Meckelein ◽  
M. Alexander Schmidt ◽  
Andreas Frey
Keyword(s):  
Cholera Toxin ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Secretory Iga ◽  
Enzyme Linked Immunosorbent Assay ◽  
Routine Diagnostics ◽  
Significant Relationships ◽  
Serum Igg ◽  
Mucosal Surfaces ◽  
Secretory Immunoglobulin

ABSTRACT Monitoring specific secretory immunoglobulin A (IgA) responses in the intestines after mucosal immunization or infection is impeded by the fact that sampling of small intestinal secretions requires invasive methods not feasible for routine diagnostics. Since IgA plasma cells generated after intragastric immunization are known to populate remote mucosal sites as well, secretory IgA responses at other mucosal surfaces may correlate to those in the intestines and could serve as proxy measures for IgA secretion in the gut. To evaluate the practicability of this approach, mice were immunized intragastrically with 0.2, 2, and 20 mg of ovalbumin plus 10 μg of cholera toxin, and the antigen-specific local secretory IgA responses in duodenal, ileal, jejunal, rectal, and vaginal secretions, saliva, urine, and feces, as well as serum IgG and IgA responses were analyzed by enzyme-linked immunosorbent assay. Correlation analysis revealed significant relationships between serum IgG and IgA, urinary IgA, salivary IgA, and secretory IgA in duodenal, jejunal, ileal, and rectal secretions for the 0.2-mg but not for the 20-mg ovalbumin dose. Fecal samples were poor predictors for intestinal antiovalbumin IgA responses, and no correlations could be established for cholera toxin, neither between local anti-cholera toxin levels nor to the antiovalbumin responses. Thus, specific IgA in serum, saliva, or urine can serve as a predictor of the release of specific IgA at intestinal surfaces after intragastric immunization, but the lack of correlations for high ovalbumin doses and for cholera toxin indicates a strong dependency on antigen type and dosage for these relationships.

scholarly journals Effects of inulin supplementation on intestinal barrier function and immunity in specific pathogen-free chickens with Salmonella infection

2020 ◽  
Vol 98 (1) ◽  
Author(s):  
Jiao Song ◽  
Qinghe Li ◽  
Nadia Everaert ◽  
Ranran Liu ◽  
Maiqing Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mucosal Immunity ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Basal Diet ◽  
Intestinal Barrier Function ◽  
Specific Pathogen Free ◽  
Specific Pathogen ◽  
Ifn Γ ◽  
Socs3 Mrna

Abstract We investigated the effects of inulin on intestinal barrier function and mucosal immunity in Salmonella enterica serovar Enteritidis (SE)–infected specific pathogen-free (SPF) chickens. SPF chickens (n = 240, 1-d-old) were divided into 4 groups (6 replicates per group, 10 chickens per replicate): a control group (CON) fed a basal diet without inulin supplementation and 3 SE-infected groups fed a basal diet supplemented with inulin 0% (SE group), 0.5% (0.5% InSE group), and 1% (1% InSE group), respectively. At 28 d of age, the chickens in SE-infected groups were orally infected with SE and in CON group were administrated with phosphated-buffered saline (PBS). Intestinal morphology, mucosal immunity, and intestinal barrier function-related gene expression were analyzed at 1- and 3-d post-infection (dpi). SE challenge significantly increased the mucosal gene expression, such as interleukin-1β (IL-1β), lipopolysaccharide-induced tumor necrosis factor factor (LITAF), interferon-γ (IFN-γ), and interleukin-6 (IL-6), and increased serum IFN-γ, secretory IgA (sIgA), and IgG concentration, and significantly decreased the gene expression levels of mucin 2 (MUC2) and claudin-1 at 3 dpi compared with the CON group (P &lt; 0.05). Inulin supplementation improved the expression levels of these immunity- and intestinal barrier function-related genes, increased villus height (VH), and decreased crypt depth (CD) in the duodenum, jejunum, and ileum at 1 and 3 dpi within the SE-challenged groups (P &lt; 0.05). SE challenge significantly increased ileal Toll-like receptor 4 (TLR4) mRNA at 1 and 3 dpi, suppressor of cytokine signaling 3 (SOCS3) mRNA at 1 dpi, and phospho-signal transducer and activator of transcription 3 (p-STAT3) and Janus kinase1 (JAK1) protein expression at 3 dpi compared with the CON group (P &lt; 0.05). Inulin supplementation suppressed p-STAT3 and JAK1 protein expression and promoted ileal TLR4 and SOCS3 mRNA expression at 3 dpi compared with SE group (P &lt; 0.05). In conclusion, inulin alleviated SE-induced gut injury by decreasing the proinflammatory response and enhancing mucosal immunity in chickens.

Microbial metabolites control the thymic development of mucosal-associated invariant T cells

Science ◽  
2019 ◽  
Vol 366 (6464) ◽  
pp. 494-499 ◽  
Author(s):  
François Legoux ◽  
Déborah Bellet ◽  
Celine Daviaud ◽  
Yara El Morr ◽  
Aurelie Darbois ◽  
...  
Keyword(s):  
T Cells ◽  
Orphan Receptor ◽  
Immune Functions ◽  
Thymic Development ◽  
Germ Free ◽  
Mait Cells ◽  
Histocompatibility Complex ◽  
Mucosal Surfaces ◽  
Mucosal Homeostasis ◽  
Antigen 5

How the microbiota modulate immune functions remains poorly understood. Mucosal-associated invariant T (MAIT) cells are implicated in mucosal homeostasis and absent in germ-free mice. Here, we show that commensal bacteria govern murine MAIT intrathymic development, as MAIT cells did not recirculate to the thymus. MAIT development required RibD expression in bacteria, indicating that production of the MAIT antigen 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) was necessary. 5-OP-RU rapidly traveled from mucosal surfaces to the thymus, where it was captured by the major histocompatibility complex class Ib molecule MR1. This led to increased numbers of the earliest MAIT precursors and the expansion of more mature receptor-related, orphan receptor γt–positive MAIT cells. Thus, a microbiota-derived metabolite controls the development of mucosally targeted T cells in a process blurring the distinction between exogenous antigens and self-antigens.

scholarly journals Molecular Characterization and Pathogenicity of Chicken Parvovirus (ChPV) in Specific Pathogen-Free Chicks Infected Experimentally

Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 606
Author(s):  
Luis Fabian N. Nuñez ◽  
Silvana H. Santander-Parra ◽  
David I. De la Torre ◽  
Lilian R. M. de Sá ◽  
Marcos R. Buim ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Genetic Characterization ◽  
Molecular Level ◽  
Molecular Characteristics ◽  
Intestinal Segments ◽  
Specific Pathogen ◽  
Infiltrating Lymphocytes ◽  
Experimental Group ◽  
Experimental Challenge

Chicken parvovirus (ChPV) is an agent frequently associated with runting stunting syndrome (RSS). This syndrome has been reported in association with ChPV in many countries, including Brazil; however, studies characterizing the virus on a molecular level are scarce, and ChPV pathogenicity in day-old chicks remains unclear. The aim of the present work was to establish the molecular characteristics of ChPV, determine the pathogenicity of ChPV in SPF chicks and detect and quantify ChPV by qPCR in several tissues and chicks of different ages. The experimental challenge was performed at one day of age, and daily and weekly observations were performed and five birds from each experimental group (mock and infected birds) were euthanized to perform the different analysis. ChPV genome copies were detected and quantified by qPCR in gut, spleen, thymus, kidney, pancreas, proventriculus and bursa. Clinically, the infected group presented with diarrhea 24 h post-infection, which persisted until 42 days of age. The small intestine was distended, and its contents were aqueous and foamy. Enteritis and dilated crypts with cyst shapes were observed in intestinal segments. Acute pancreatitis associated with lymphocytic nodules, infiltrating lymphocytes and plasma cells between the pancreatic acinus was observed. Koch’s postulate was demonstrated and the genetic characterization of the VP1 gene showed that the Brazilian ChPV isolate belongs to the ChPV II group.

scholarly journals Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice

2012 ◽  
Vol 303 (11) ◽  
pp. G1288-G1295 ◽  
Author(s):  
Yasunari Asano ◽  
Tetsuya Hiramoto ◽  
Ryo Nishino ◽  
Yuji Aiba ◽  
Tae Kimura ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Critical Role ◽  
Coli Strain ◽  
Biologically Active ◽  
Free Form ◽  
Mammalian Host ◽  
Loop Model ◽  
Glucuronidase Activity ◽  
Specific Pathogen

There is increasing interest in the bidirectional communication between the mammalian host and prokaryotic cells. Catecholamines (CA), candidate molecules for such communication, are presumed to play an important role in the gut lumen; however, available evidence is limited because of the lack of actual data about luminal CA. This study evaluated luminal CA levels in the gastrointestinal tract and elucidated the involvement of gut microbiota in the generation of luminal CA by comparing the findings among specific pathogen-free mice (SPF-M), germ-free mice (GF-M), and gnotobiotic mice. Substantial levels of free dopamine and norepinephrine were identified in the gut lumen of SPF-M. The free CA levels in the gut lumen were lower in GF-M than in SPF-M. The majority of CA was a biologically active, free form in SPF-M, whereas it was a biologically inactive, conjugated form in GF-M. The association of GF-M with either Clostridium species or SPF fecal flora, both of which have abundant β-glucuronidase activity, resulted in the drastic elevation of free CA. The inoculation of E. coli strain into GF-M induced a substantial amount of free CA, but the inoculation of its mutant strain deficient in the β-glucuronidase gene did not. The intraluminal administration of DA increased colonic water absorption in an in vivo ligated loop model of SPF-M, thus suggesting that luminal DA plays a role as a proabsorptive modulator of water transport in the colon. These results indicate that gut microbiota play a critical role in the generation of free CA in the gut lumen.

scholarly journals The mucosal barrier: Protective frontier to the outside world

2011 ◽  
Vol 33 (4) ◽  
pp. 10-15
Author(s):  
Tony Corfield
Keyword(s):  
External Environment ◽  
The Body ◽  
Mucosal Barrier ◽  
Mucosal Protection ◽  
Protective Barrier ◽  
Pathological Conditions ◽  
Mucosal Surfaces ◽  
Microbiological Agents ◽  
Gut Metabolism

The mucosal surfaces throughout the body are designed to provide an interface which can tolerate and protect at the same time. They need to screen the external environment and select for transport of required factors, such as nutrients from the diet, interact with the microflora present – taking benefit from those commensal strains while resisting pathogens, act as a milieu for an assortment of antimicrobial molecules and also combat attack from aggressive chemical and other microbiological agents. The system must be dynamic so that a continuous intact protective barrier is maintained at all times. Failure of the barrier leads to pathological conditions, and abnormal barrier components are among well known biomarkers for mucosal diseases. This brief review highlights some of the aspects relating to gut metabolism and mucosal protection.

scholarly journals Longan Pulp Polysaccharide Protects Systemic Immunity and Intestinal Immunity in Mice Induced by Cyclophosphamide

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 738-738
Author(s):  
Yajuan Bai ◽  
Mingwei Zhang
Keyword(s):  
Mucosal Immunity ◽  
Plasma Cells ◽  
Underlying Mechanism ◽  
Secretory Component ◽  
Secretory Iga ◽  
Intestinal Lumen ◽  
Mucosal Barrier ◽  
Intestinal Immunity ◽  
Systemic Immunity ◽  
Serum Iga

Abstract Objectives This study aimed to explore the effect of longan pulp polysaccharide (LP) on the systemic immunity and intestinal mucosal immunity with immunosuppressive mice. The synthesis processing and secretion of intestinal secretory IgA (SIgA) were investigated. Methods Serum IgA, IgG, IgM and intestinal SIgA were detected by ELISA. Genes involved in the synthesis and secretion of SIgA were detected by Q-PCR and western blot. Results LP increased the thymus index, spleen index, and serum IgA level in cyclophosphamide (CTX)-treated mice. SIgA secretion in intestinal lumen was increased by LP as well. The underlying mechanism comes down to the facts as follows: LP increased intestinal cytokines expression and TGFβRII that is associated with pathways of IgA class switch recombination (CSR). By improving protein expression of mucosal address in cell-adhesion molecule-1 (MAdCAM-1) and integrin α4β7, LP was beneficial to gut homing of IgA + plasma cells. LP increased IgA, polymeric immunoglobulin receptor (pIgR), and secretory component (SC) to fortify the SIgA secretion. Conclusions This study suggested that moderate consumption of LP is helpful for improving systemic immunity and intestinal mucosal immunity via promotion of intestinal SIgA to strengthen the mucosal barrier. Funding Sources This work was supported by the National Key Research Project of China (2018YFC1602105, 2019YFD1002304), Guangdong Provincial Science and Technology Project (2018A050506050), President Foundation of Guangdong Academy of Agricultural Sciences (201812B).

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