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.

scholarly journals Characterization of a Lactococcus lactis Strain That Secretes a Major Epitope of Bovine Beta-Lactoglobulin and Evaluation of Its Immunogenicity in Mice

2003 ◽  
Vol 69 (11) ◽  
pp. 6620-6627 ◽  
Author(s):  
Jean-Marc Chatel ◽  
Sebastien Nouaille ◽  
Karine Adel-Patient ◽  
Yves Le Loir ◽  
Herman Boe ◽  
...  
Keyword(s):  
Immune Response ◽  
Fusion Protein ◽  
Lactococcus Lactis ◽  
Immunoglobulin E ◽  
Specific Ige ◽  
Specific Immune Response ◽  
Lactis Strain ◽  
Beta Lactoglobulin ◽  
Β Lactoglobulin

ABSTRACT Bovine β-lactoglobulin (Blg) is one of the major cow's milk allergens. Peptide 41-60 of Blg (Blg41-60) was described as a murine T-cell determinant and a murine, rat, and human immunoglobulin E (IgE) epitope. The aim of this study was the expression of Blg41-60 as a fusion protein in the food-grade bacterium Lactococcus lactis and the characterization of its immunogenicity in mice. We constructed a recombinant strain of L. lactis capable of inducible production and secretion of Blg41-60::Nuc, a fusion protein between Blg41-60 and the mature part of the staphylococcal nuclease (Nuc). The highest production yield of Blg41-60::Nuc (32.5 mg/liter) was reached 4 h after induction. At this time, up to 75% of Blg41-60::Nuc was secreted. When monoclonal antibodies specific for Blg41-60 were used, purified Blg41-60::Nuc and synthetic Blg41-60 exhibited very similar immunoreactivities. Subcutaneous coadministration of purified Blg41-60::Nuc and killed nonrecombinant L. lactis resulted in the induction of specific anti-Blg41-60 IgG2a and IgG1. The IgG1/IgG2a ratio and the lack of specific IgE suggest a Th1-type immune response, i.e., a nonallergic response. Similar administrations of the killed Blg41-60::Nuc-producing L. lactis strain did not elicit a specific immune response, whereas a transitory mucosal IgA-specific immune response was induced in mice after oral administration of the live Blg41-60::Nuc-producing L. lactis strain.

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 Receptor-Dependent Immune Responses in Pigs after Oral Immunization with F4 Fimbriae

1999 ◽  
Vol 67 (2) ◽  
pp. 520-526 ◽  
Author(s):  
Wim Van den Broeck ◽  
Eric Cox ◽  
Bruno M. Goddeeris
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Oral Immunization ◽  
Mucosal Immune Response ◽  
Mucosal Protection ◽  
Mucosal Immunization ◽  
Oral Vaccines ◽  
Booster Immunization ◽  
Iga Antibodies ◽  
Etec Infection

ABSTRACT F4 receptor-positive (F4R+) and F4 receptor-negative (F4R−) pigs were orally vaccinated with purified F4 fimbriae of enterotoxigenic Escherichia coli (ETEC). Serum immunoglobulin G (IgG) and IgA responses were readily detected in F4R+ animals, whereas immune responses were not detected in F4R− animals. Even after a subsequent oral infection with virulent F4+ ETEC and a booster immunization with F4, the F4R− animals remained F4 seronegative whereas the unvaccinated F4R+ pigs exhibited clear IgA and IgG responses. These results clearly demonstrate that F4Rs are a prerequisite for an immune response following oral immunization. Furthermore, indications that oral F4 vaccination can induce mucosal protection were obtained, since the experimental ETEC infection did not induce a systemic booster response or fecal ETEC excretion in orally vaccinated F4R+ pigs, in contrast to the clear immune response and ETEC excretion of unvaccinated F4R+ animals. F4-specific IgA antibodies could be found in the feces of the vaccinated F4R+ pigs. They are secreted at the intestinal mucosal surface and appear to prevent ETEC infection. The F4R-dependent induction of a mucosal immune response can be used as a model to better understand mucosal immunization and mucosal immune responses and can contribute to the development of oral vaccines in veterinary as well as in human medicine.

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 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 Bovine Rotavirus Nonstructural Protein 4 Produced by Lactococcus lactis Is Antigenic and Immunogenic

2001 ◽  
Vol 67 (4) ◽  
pp. 1423-1428 ◽  
Author(s):  
Vincent Enouf ◽  
Philippe Langella ◽  
Jacqueline Commissaire ◽  
Jean Cohen ◽  
Gérard Corthier
Keyword(s):  
Escherichia Coli ◽  
Immune Response ◽  
Lactococcus Lactis ◽  
Nonstructural Protein ◽  
Biological Effects ◽  
Expression System ◽  
Bovine Rotavirus ◽  
Viral Antigens ◽  
Secretion Efficiency ◽  
Insight Into

ABSTRACT Rotavirus nonstructural protein 4 (NSP4) can induce diarrhea in mice. To get insight into the biological effects of NSP4, production of large quantities of this protein is necessary. We first tried to produce the protein in Escherichia coli, but thensp4 gene proved to be unstable. The capacity of the generally regarded as safe organism Lactococcus lactis to produce NSP4 either intra- or extracellularly was then investigated by using the nisin-controlled expression system. Production of recombinant NSP4 (rNSP4) was observed in L. lactis for both locations. In spite of a very low secretion efficiency, the highest level of production was obtained with the fusion between a lactococcal signal peptide and rNSP4. Cultures of the rNSP4-secreting strain were injected into rabbits, and a specific immune response was elicited. The anti-rNSP4 antibodies produced in these rabbits recognized NSP4 in MA104 cells infected by rotavirus. We showed that L. lactisis able to produce antigenic and immunogenic rNSP4 and thus is a good organism for producing viral antigens.

scholarly journals Secretory immunoglobulin A of the respiratory system and COVID-19

2021 ◽  
Vol 31 (6) ◽  
pp. 792-798
Author(s):  
Nadezhda O. Kryukova ◽  
Ekaterina B. Rakunova ◽  
M. P. Kostinov ◽  
Irina A. Baranova ◽  
Oxana A. Svitich
Keyword(s):  
Immune Response ◽  
Respiratory Tract ◽  
Mucosal Immunity ◽  
Immunoglobulin A ◽  
Disease Diagnosis ◽  
Mucosal Immune Response ◽  
Secretory Iga ◽  
Published Data ◽  
Antibody Isotype ◽  
Treatment And Prevention

The main focus in the course of COVID-19 goes on assessing the overall immune response. The role of mucosal immunity in this disease has not been studied sufficiently.The study aimed to analyze published data about secretory IgA as a significant indicator of the mucosal immune response of the respiratory tract in the context of the COVID-19 pandemic.Methods. Articles were identified via PubMed bibliographic database. The time-span of research was two years (2020, 2021).Results. The search identified 54 articles. There is evidence that secretory IgA (sIgA) is the main antibody isotype of the mucosal immunity. It is produced in quantities significantly higher than those of all other isotypes of immunoglobulins combined. sIgA antibodies are effective against various pathogens, including the SARS-CoV-2 virus, due to mechanisms such as neutralization, suppression of adhesion to the mucosal surface and invasion of epithelial cells, agglutination and facilitating the removal of pathogenic microorganisms with the mucosal secretions. Virus-specific IgA antibodies in the blood serum are detected in patients with COVID-19 as early as two days after the first symptoms, while IgM or IgG class antibodies appear only after 5 days. We accessed the efficacy of intranasal immunization as to induction of predominant production of sIgA in the upper and lower respiratory tract.Conclusion. The current information on the local immune response of the respiratory mucosa is important for understanding the pathophysiological mechanisms of the disease, diagnosis, and development of new methods of treatment and prevention of COVID-19.

scholarly journals The Wanderings of Gut-Derived IgA Plasma Cells: Impact on Systemic Immune Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Selina J. Keppler ◽  
Marie Christine Goess ◽  
Julia M. Heinze
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
B Cell ◽  
Protective Immunity ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Commensal Microbiota ◽  
Mucosal Tissues ◽  
Iga Antibodies ◽  
Antibody Secreting Cells

Humoral immunity is mainly mediated by a B cell population highly specialized to synthesize and secrete large quantities of antibodies – the antibody-secreting cells (ASC). In the gastrointestinal environment, a mixture of foreign antigens from the diet, commensal microbiota as well as occasional harmful pathogens lead to a constant differentiation of B cells into ASC. Due to this permanent immune response, more than 80% of mammalian ASC reside in the gut, of which most express immunoglobulin A (IgA). IgA antibodies contribute to intestinal homeostasis and can mediate protective immunity. Recent evidence points at a role for gut-derived ASC in modulating immune responses also outside of mucosal tissues. We here summarize recent evidence for wandering ASC, their antibodies and their involvement in systemic immune responses.

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