scholarly journals Gut Colonization of Mice withactA-Negative Mutant of Listeria monocytogenesCan Stimulate a Humoral Mucosal Immune Response

2001 ◽  
Vol 69 (6) ◽  
pp. 3542-3549 ◽  
Author(s):  
Muniraj Manohar ◽  
Donald O. Baumann ◽  
Nicolaas A. Bos ◽  
John J. Cebra
Keyword(s):  
Immune Response ◽  
Immunoglobulin A ◽  
Mucosal Immune Response ◽  
Oral Infection ◽  
Significant Rise ◽  
Intestinal Lumen ◽  
Mesenteric Lymph Nodes ◽  
Marked Rise ◽  
Gut Colonization ◽  
Iga Production

ABSTRACT We used Listeria monocytogenes, a gram-positive, facultative intracellular bacterium, to study the gut mucosal immune responses following oral infection. We employed a germfree (GF) mouse model to try to accentuate the development of a humoral mucosal immune response in the gut, and we used oral colonization with one of the mutants, actA-negative (ΔactA) L. monocytogenes, to restrict infection largely to the gut. The ΔactA mutant was able to colonize the intestinal mucosa of formerly GF mice for long periods of time without causing disease while eliciting secretory immunoglobulin A (IgA) responses, as evidenced by gut tissue fragment culture assays. Flow cytometric analyses and immunohistochemical methods showed the development of only minimal germinal center reactions (GCR) in Peyer's patches and more robust GCR in mesenteric lymph nodes. Pronounced increases in total (natural) IgA production occurred in gut tissues by day 7 and were maintained for up to 90 days. Levels of specific IgA were modest in gut tissues on day 14, increased until day 76, and stabilized at day 90. We also observed a significant rise in serum IgA and IgG1 levels following oral infection by listeriae. Upon colonization, the organisms mainly infected the intestines and intestinal lumen, and we only sporadically observed few colony-forming bacteria in the liver and spleen. We observed a marked rise in IgA-secreting cells, including listeria-specific IgA antibody-secreting cells, in the lamina propria of the small intestine by enzyme-linked immunospot assays. To ascertain whether some of the IgA was specific for listeriae, we performed Western blot analysis to test the reactivity of IgA from fragment cultures to antigens in sonicates of L. monocytogenes. We detected IgA binding to antigenic proteins with molecular masses of 96, 60, 40, and 14 kDa in theListeria sonicates.

scholarly journals Cellular and molecular changes and immune response in the intestinal mucosa during Trichinella spiralis early infection in rats

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
María Priscila Saracino ◽  
Cecilia Celeste Vila ◽  
Melina Cohen ◽  
María Virginia Gentilini ◽  
Guido Hernán Falduto ◽  
...  
Keyword(s):  
Immune Response ◽  
Lamina Propria ◽  
Trichinella Spiralis ◽  
Mucosal Immune Response ◽  
Mesenteric Lymph Nodes ◽  
Muscle Larvae ◽  
Gut Immunity ◽  
Gut Mucosa

Abstract Background: The main targets of the host’s immune system in Trichinella spiralis infection are the adult worms (AW), at the gut level, and the migrant or newborn larvae (NBL), at systemic and pulmonary levels. Most of the studies carried out in the gut mucosa have been performed on the Payer’s patches and/or the mesenteric lymph nodes but not on the lamina propria, therefore, knowledge on the gut immune response against T. spiralis remains incomplete. Methods This study aimed at characterizing the early mucosal immune response against T. spiralis, particularly, the events taking place between 1 and 13 dpi. For this purpose, Wistar rats were orally infected with muscle larvae of T. spiralis and the humoral and cellular parameters of the gut immunity were analysed, including the evaluation of the ADCC mechanism exerted by lamina propria cells. Results A marked inflammation and structural alteration of the mucosa was found. The changes involved an increase in goblet cells, eosinophils and mast cells, and B and T lymphocytes, initially displaying a Th1 profile, characterised by the secretion of IFN-γ and IL-12, followed by a polarization towards a Th2 profile, with a marked increase in IgE, IgG1, IL-4, IL-5 and IL-13 levels, which occurred once the infection was established. In addition, the helminthotoxic activity of lamina propria cells demonstrated the role of the intestine as a place of migrant larvae destruction, indicating that not all the NBLs released in the gut will be able to reach the muscles. Conclusions The characterization of the immune response triggered in the gut mucosa during T. spiralis infection showed that not only an effector mechanism is directed toward the AW but also towards the NBL as a cytotoxic activity was observed against NBL exerted by lamina propria cells.

scholarly journals The Inflammatory Processes Driven by Gut Microbiota

Acta Medica ◽  
2021 ◽  
pp. 1-9
Author(s):  
Ayşe Buruş ◽  
Başak Çeltikçi ◽  
Yasemin Aksoy
Keyword(s):  
Immune Response ◽  
Bacterial Translocation ◽  
Immune Modulation ◽  
Immunoglobulin A ◽  
Intestinal Lumen ◽  
Mucosal Barrier ◽  
Gastrointestinal Microbiota ◽  
Inflammatory Processes ◽  
T Cell Regulation ◽  
Inflammatory Bowel

Microbiome studies have shown alterations in bacterial communities in the state of many diseases, including inflammatory bowel disease, metabolic disorders, autoimmune diseases, neurodegenerative diseases, and cancer. Chronic inflammation is a common promoter of many of these pathological processes. Shifting in the microbial diversity is also known as dysbiosis. Dysbiosis, increased detrimental bacterial products, decreased favorable microbial metabolites, interrupted tissue barriers, and bacterial translocation cause excessive immune response and inflammation. Several mechanisms play a role to maintain intestinal homeostasis by limiting bacterial translocation from the intestinal lumen into the lamina propria. Among these mechanisms, most importantly, the mucosal barrier that consists of the antimicrobial peptides, mucus, and immunoglobulin A is fundamental to protect epithelial barrier integrity to reduce the excessive immune response. Moreover, recognizing bacteria and metabolites through receptors results in T cell regulation and immune modulation, which is the keystone of the controlled immune response. This review summarizes the anti-inflammatory and pro-inflammatory mechanisms driven by gastrointestinal microbiota, and it also highlights the recent approaches, including epigenetics and precision medicine.

scholarly journals The mucosal immune system and IgA nephropathy

2021 ◽  
Author(s):  
Loreto Gesualdo ◽  
Vincenzo Di Leo ◽  
Rosanna Coppo
Keyword(s):  
Immune Response ◽  
Mucosal Immunity ◽  
Lymphoid Tissue ◽  
Genetic Factors ◽  
Immunoglobulin A ◽  
Mucosal Immune Response ◽  
Immunoglobulin A Nephropathy ◽  
Food Antigen ◽  
The Relationship

Abstract The precise pathogenesis of immunoglobulin A nephropathy (IgAN) is still not clearly established but emerging evidence confirms a pivotal role for mucosal immunity. This review focuses on the key role of mucosa-associated lymphoid tissue (MALT) in promoting the onset of the disease, underlying the relationship among microbiota, genetic factors, food antigen, infections, and mucosal immune response. Finally, we evaluate potential therapies targeting microbes and mucosa hyperresponsiveness in IgAN patients.

scholarly journals Segmented Filamentous Bacteria Are Potent Stimuli of a Physiologically Normal State of the Murine Gut Mucosal Immune System

1999 ◽  
Vol 67 (4) ◽  
pp. 1992-2000 ◽  
Author(s):  
Gwen L. Talham ◽  
Han-Qing Jiang ◽  
Nicolaas A. Bos ◽  
John J. Cebra
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immunoglobulin A ◽  
Mucosal Immune System ◽  
Filamentous Bacteria ◽  
Mesenteric Lymph Nodes ◽  
Segmented Filamentous Bacteria ◽  
Iga Antibody ◽  
Autochthonous Bacteria ◽  
Iga Production

ABSTRACT Segmented filamentous bacteria (SFB) are autochthonous bacteria inhabiting the intestinal tracts of many species, including humans. We studied the effect of SFB on the mucosal immune system by monoassociating formerly germfree C3H/HeN mice with SFB. At various time points during 190 days of colonization, fragment cultures of small intestine and Peyer’s patches (PP) were analyzed for total immunoglobulin A (IgA) and SFB-specific IgA production. Also, phenotypic changes indicating germinal center reactions (GCRs) and the activation of CD4+ T cells in PP were determined by using fluorescence-activated cell sorter analyses. A second group of SFB-monoassociated mice was colonized with a gram-negative commensal,Morganella morganii, to determine if the mucosal immune system was again stimulated and to evaluate the effect of prior colonization with SFB on the ability of M. morganii to translocate to the spleen and mesenteric lymph nodes. We found that SFB stimulated GCRs in PP from day 6 after monoassociation, that GCRs only gradually waned over the entire length of colonization, that natural IgA production was increased to levels 24 to 63% of that of conventionally reared mice, and that SFB-specific IgA was produced but accounted for less than 1.4% of total IgA. Also, the proportion of CD4+, CD45RBlow T cells, indicative of activated cells, gradually increased in the PP to the level found in conventionally reared mice. Secondary colonization with M. morganii was able to stimulate GCRs anew, leading to a specific IgA antibody response. Previous stimulation of mucosal immunity by SFB did not prevent the translocation of M. morganii in the double-colonized mice. Our findings generally indicate that SFB are one of the single most potent microbial stimuli of the gut mucosal immune system.

scholarly journals Mucosal Immune Response in Nasal-Associated Lymphoid Tissue upon Intranasal Administration by Adjuvants

2018 ◽  
Vol 10 (5-6) ◽  
pp. 515-521 ◽  
Author(s):  
Hiromi Takaki ◽  
Shingo Ichimiya ◽  
Misako Matsumoto ◽  
Tsukasa Seya
Keyword(s):  
Immune Response ◽  
Nasal Cavity ◽  
Lymphoid Tissue ◽  
Natural Infection ◽  
Mucosal Immune Response ◽  
T Cell Response ◽  
Nasal Administration ◽  
Upper Respiratory Tract ◽  
Tract Infections ◽  
Iga Production

The nasal administration of vaccines directed against diseases caused by upper respiratory tract infections of pathogens, such as the influenza virus, mimics the natural infection of pathogens and induces immunoglobulin A (IgA) production in the nasal cavity to effectively protect viral entry. Therefore, the development of a nasally administered vaccine is a research objective. Because the antigenicity of influenza split vaccines is low, nasal inoculation with the vaccine alone does not induce strong IgA production in the nasal cavity. However, the addition of adjuvants activates the innate immune response, enhancing antigen-specific IgA production and the T-cell response. Although the development of suitable adjuvants for nasal vaccinations is in progress, the mechanism by which adjuvants promote the immune response is still unclear. In this review, we discuss the mucosal immune response, especially in the nasal-associated lymphoid tissue, induced in response to the intranasal inoculation of an influenza vaccine and adjuvants in animal models.

scholarly journals The Potential Role of an Aberrant Mucosal Immune Response to SARS-CoV-2 in the Pathogenesis of IgA Nephropathy

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 881
Author(s):  
Zhao Zhang ◽  
Guorong Zhang ◽  
Meng Guo ◽  
Wanyin Tao ◽  
Xingzi Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Iga Nephropathy ◽  
Early Stage ◽  
Elevated Serum ◽  
Serum Levels ◽  
Mucosal Immune Response ◽  
Elevated Concentration ◽  
Protein Receptor ◽  
Iga Production ◽  
Antibody Levels

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global concern. Immunoglobin A (IgA) contributes to virus neutralization at the early stage of infection. Longitudinal studies are needed to assess whether SARS-CoV-2-specific IgA production persists for a longer time in patients recovered from severe COVID-19 and its lasting symptoms that can have disabling consequences should also be alerted to susceptible hosts. Here, we tracked the anti-SARS-CoV-2 spike protein receptor-binding domain (RBD) antibody levels in a cohort of 88 COVID-19 patients. We found that 52.3% of the patients produced more anti-SARS-CoV-2 RBD IgA than IgG or IgM, and the levels of IgA remained stable during 4–41 days of infection. One of these IgA-dominant COVID-19 patients, concurrently with IgA nephropathy (IgAN), presented with elevated serum creatinine and worse proteinuria during the infection, which continued until seven months post-infection. The serum levels of anti-SARS-CoV-2 RBD and total IgA were higher in this patient than in healthy controls. Changes in the composition of the intestinal microbiota, increased IgA highly coated bacteria, and elevated concentration of the proinflammatory cytokine IL-18 were indicative of potential involvement of intestinal dysbiosis and inflammation to the systemic IgA level and, consequently, the disease progression. Collectively, our work highlighted the potential adverse effect of the mucosal immune response to SARS-CoV-2 infection, and that additional care should be taken with COVID-19 patients presenting with chronic diseases such as IgAN.

scholarly journals Comparison of the Antibodies in Lymphocyte Supernatant and Antibody-Secreting Cell Assays for Measuring Intestinal Mucosal Immune Response to a Novel Oral Typhoid Vaccine (M01ZH09)

2005 ◽  
Vol 12 (9) ◽  
pp. 1127-1129 ◽  
Author(s):  
B. D. Kirkpatrick ◽  
Matthew D. Bentley ◽  
Anette M. Thern ◽  
Catherine J. Larsson ◽  
Cassandra Ventrone ◽  
...  
Keyword(s):  
Immune Response ◽  
Peripheral Blood ◽  
Immunoglobulin A ◽  
Mucosal Immune Response ◽  
Peripheral Blood Lymphocytes ◽  
Typhoid Vaccine ◽  
Secreting Cell ◽  
Antibody Secreting Cell ◽  
Cell Assays ◽  
Enteric Infections

ABSTRACT Antibody-secreting cell (ASC) and antibodies in lymphocyte supernatant (ALS) assays are used to assess intestinal mucosal responses to enteric infections and vaccines. The ALS assay, performed on cell supernatants, may represent a convenient alternative to the more established ASC assay. The two methods, measuring immunoglobulin A to Salmonella enterica serovar Typhi lipopolysaccharide, were compared in volunteers vaccinated with a live-attenuated typhoid vaccine M01ZH09. The specificity of the ALS assay compared to the ASC assay was excellent (100%), as was sensitivity (82%). The ALS assay was less sensitive than the ASC assay at ≤42 spots/106 peripheral blood lymphocytes.

scholarly journals Induction of Mucosal Immune Response after Intranasal or Oral Inoculation of Mice with Lactococcus lactis Producing Bovine Beta-Lactoglobulin

2001 ◽  
Vol 8 (3) ◽  
pp. 545-551 ◽  
Author(s):  
Jean-Marc Chatel ◽  
Philippe Langella ◽  
Karine Adel-Patient ◽  
Jacqueline Commissaire ◽  
Jean-Michel Wal ◽  
...  
Keyword(s):  
Immune Response ◽  
Lactococcus Lactis ◽  
Expression System ◽  
Immunoglobulin A ◽  
Mucosal Immune Response ◽  
Delivery Vehicle ◽  
Gene Encoding ◽  
Oral Inoculation ◽  
Iga Antibodies ◽  
Beta Lactoglobulin

ABSTRACT The bovine beta-lactoglobulin (BLG) is a major cow's milk allergen. Here, we evaluated the immune response against BLG induced in mice, using the organism Lactococcus lactis, which has GRAS (“generally regarded as safe”) status, as a delivery vehicle. The cDNA of the blg gene, encoding BLG, was expressed and engineered for either intra- or extracellular expression inL. lactis. Using a constitutive promoter, the yield of intracellular recombinant BLG (rBLG) was about 20 ng per ml of culture. To increase the quantity of rBLG, the nisin-inducible expression system was used to produce rBLG in the cytoplasmic and extracellular locations. Although the majority of rBLG remained in the cytoplasm, the highest yield (2 μg per ml of culture) was obtained with a secreting strain that encodes a fusion between a lactococcal signal peptide and rBLG. Whatever the expression system, the rBLG is produced mostly in a soluble, intracellular, and denatured form. The BLG-producing strains were then administered either orally or intranasally to mice, and the immune response to BLG was examined. Specific anti-BLG immunoglobulin A (IgA) antibodies were detected 3 weeks after the immunization protocol in the feces of mice immunized with the secreting lactococcal strain. Specific anti-BLG IgA detected in mice immunized with lactococci was higher than that obtained in mice immunized with the same quantity of pure BLG. No specific anti-BLG IgE, IgA, IgG1, or IgG2a was detected in sera of mice. These recombinant lactococcal strains constitute good vehicles to induce a mucosal immune response to a model allergen and to better understand the mechanism of allergy induced by BLG.

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