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At least 649 records · Page 36Linked to original sources
PubMed2003

Mucosal immunization with inactivated HIV-1-capturing nanospheres induces a significant HIV-1-specific vaginal antibody response in mice.

Mucosal secretory IgA is considered to have an important role in the prevention of human immunodeficiency virus type 1 (HIV-1) transmission through sexual intercourse. Therefore, substances that induce HIV-1-specific IgA antibody in the genital tract may become promising candidates for prophylactic vaccine against HIV-1 infection. We have previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and gp120 antigens on their surface and that intravaginal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody in mice. In this study, various strategies for immunization with HIV-NS were undertaken to induce HIV-1-specific IgA response in the mouse genital tract. HIV-NS were administered intravaginally, orally, intranasally or intraperitoneally to mice. Progesterone treatment enhanced the anti-HIV-1 IgA response to intravaginal immunization significantly, but intranasal immunization with HIV-NS was more effective compared with other immunization routes in terms of vaginal IgA response. In addition, vaginal washes from intranasally immunized mice were capable of neutralizing HIV-1(IIIB). Thus, application of HIV-NS is a practical approach to promote HIV-1-specific IgA response by the vaginal mucosa in the mouse and intranasal appears to be an effective immunization route in this animal model. Intranasal immunization with HIV-NS should be further pursued for its potential as an HIV-1 prophylactic vaccine.

AIDS Vaccines↗
PubMed2026

Genome-wide Identification and Expression Profiling Reveal the Galectin Gene Family Diversity and their Possible Role in Antibacterial Mucosal Immunity in Japanese Flounder (Paralichthys olivaceus).

Galectins are a family of proteins that bind specifically to β-galactosides. Their importance in innate immunity of mammals has been well-documented. However, the systematic identification and characterization of galectin gene family remain limited in teleost. In this study, we identified 13 galectin genes (lgals2, lgals2a, lgals2b, lgals3, lgals3a, lgals3b, lgals4, lgals8, lgals8a, lgals9, grp, grp-b, grp-c) from Paralichthys olivaceus genome and analyzed their tissue expressions and expressions in response to Gram-negative and Gram-positive bacterial infections in mucosal tissues (gills, intestine and skin). The P. olivaceus galections were classified into three distinct types based on carbohydrate recognition domains (CRDs). Phylogenetic and syntenic analyses revealed that these galectins are closely related to their counterparts in turbot and zebrafish. Moreover, the transcripts of the 13 galectins were widespread across all tested tissues of healthy fish and regulated following challenge with Vibrio anguillarum or Streptococcus iniae in mucosal tissues, indicating their involvement in P. olivaceus immune response to bacterial infections. The lgals2a was significantly upregulated in the three mucosal tissues by either bacterial infection, whereas lgals9 and grp were basically downregulated in these tissues by either infection. On the other hand, the lgals3b and lgals4 exhibited a bacteria-specific responsive expression as they were upregulated by V. anguillarum whereas remained stable upon S. iniae infection in the gills. We also observed a positive correlation between expression level and bacterial load for the upregulated galectin genes and a negative correlation for the downregulated galectin genes. These results suggest a functional divergence among galectin members in mucosal immunity against bacterial infection in P. olivaceus.

Animals↗
PubMedDate not supplied

Nutritional modulation of intestinal mucosal immunity.

Protein-energy malnutrition results in an increased risk of gastrointestinal infection. This can be attributed in part to impaired immune responses. Cell-mediated immunity is decreased as judged by reduced number and function of thymus-dependent lymphocytes, impaired delayed cutaneous hypersensitivity reactions, and decreased production of lymphokines. Concentration of secretory IgA is reduced and there are fewer intraepithelial lymphocytes. Antibody responses following viral vaccine administration are reduced and there is decrease in natural killer cell activity. In addition, the number of bacteria binding to epithelial cells is increased. These changes are observed also in certain selected nutrient deficiencies, such as that of vitamin A. It is suggested that impaired systemic and mucosal immunity contributes to the increased frequency and severity of intestinal infections seen in undernourished individuals.

Animals↗
PubMedDate not supplied

Perturbation of mucosal immune defence mechanisms by bacterial IgA proteases.

The secretory IgA system plays an important role in protecting the mucous membranes of the respiratory tract from attacks by microorganisms and potential allergens. We present evidence of in vivo cleavage of S-IgA1 in nasopharyngeal secretions by IgA1 proteases excreted by certain bacteria colonizing the upper respiratory tract. A procedure in two stages, which includes separation of secretion constituents by HPLC and subsequent immunochemical analysis of the fractions by two ELISA systems, identified the S-IgA fragments observed in some nasopharyngeal secretions as intact (FC alpha)2 . SC and Fab alpha, respectively. It is conceivable that colonization of areas of the respiratory tract by increased numbers of IgA1 protease-producing bacteria might cause a local impairment of the mucosal immune barrier. It is hypothesized that such bacterium-induced changes may be a primary event in the pathogenesis of certain inflammatory respiratory diseases and some forms of atopy.

Bacteria↗
PubMed1994

Systemic and mucosal immunity induced by BCG vector expressing outer-surface protein A of Borrelia burgdorferi.

The bacillus Calmette-Guerin (BCG) is a live attenuated strain of Mycobacterium bovis which offers potential advantages as a vector for mucosal delivery of antigens. Recombinant BCG elicits protective humoral immune responses to a variety of antigens. Furthermore, BCG binds specifically to microfold cells present in the epithelium overlying lymphoid follicles throughout the mucosal immune system. Here we show that a single intranasal vaccination with recombinant BCG expressing the outer-surface protein A antigen from B. burgdorferi results in a prolonged (more than one year) protective systemic IgG response and a highly sustained secretory IgA response which is disseminated throughout the mucosal immune system. Furthermore, intranasal immunization induces marked, organized lymphocyte accumulation in the proximal nasopharyngeal lymphoid tissue as well as at distal mucosal sites; the appearance and persistence of lymphoid aggregates correlates with the secretory immune responses. Thus intranasal immunization with recombinant BCG is a powerful method for inducing long-lasting secretory and systemic immune responses.

Administration, Intranasal↗
PubMed1995

Mucosal immune response to Helicobacter pylori and cytotoxic mechanism.

BACKGROUND: Helicobacter pylori is widely accepted as a major pathogen in gastritis. The histologic features of H. pylori gastritis are the numerous infiltrating mononuclear cells (MNCs) and neutrophils. It is not clear what role the infiltrating MNCs and neutrophils play in H. pylori gastritis. METHODS: In this study, we have established enzyme-linked immunospot (ELISPOT) assay for the measurement of H. pylori antibody-producing cells in gastric mucosa. RESULTS: Using ELISPOT assay, we found that H. pylori-specific IgA-producing cells as well as IgG-producing cells were distributed in gastric mucosa. These H. pylori-specific antibodies in gastric mucosa and neutrophils are responsible for the induction of cytotoxic effect to cultured Vero cells. CONCLUSIONS: These observations suggest that a mucosal immune response specific to H. pylori is closely associated with the pathogenesis of gastritis.

Animals↗
PubMed1990

Mucosal immunity in adult primary glomerulonephritis. I. Evaluation of salivary IgA subclasses and components.

Salivary components (proteins, albumin, IgA1, IgA2, IgG, IgM, beta 2-microglobulin, neopterin and peroxidase) were investigated in 3 adult types of primary glomerulonephritis (PGN): IgA mesangial glomerulonephritis (IgAGN; n = 14); idiopathic membranous glomerulonephritis (n = 8); idiopathic nephrotic syndrome (INS; n = 14), and a control group (n = 11). Salivary IgA1 levels were significantly increased in all these PGN whereas salivary IgA2 levels were only higher than controls in INS. Albumin and proteins did not differ between PGN and controls, while the IgA1 + IgA2/protein ratio was significantly increased in these 3 PGN. Salivary neopterin levels were enhanced in the 3 types of PGN, whereas beta 2-microglobulin levels were not. The other salivary components did not differ from controls. These results demonstrate the nonspecificity of the IgA increase at mucosal sites previously found in IgAGN and raise the hypothesis of an activation of mucosal immunity of PGN or of a disturbed isotypic network or lymphokine secretion in these diseases.

Adult↗
PubMedDate not supplied

Glutamine peptide does not improve gut barrier function and mucosal immunity in total parenteral nutrition.

In two separate experiments, three groups of 10 (first experiment) and 12 (second experiment) rats each were catheterized for the long term via the right jugular vein and fed one of the following dietary regimens for 7 days while in individual metabolism cages. The rat food control groups were fed powdered rat food. The total parenteral nutrition (TPN) formula for one group was enriched with the stable dipeptide L-alanyl-L-glutamine (ALA-GLN) equivalent to a 1% or 2% glutamine concentration. For the control TPN groups, the dipeptide was replaced by isonitrogenous amounts of alanine (ALA). In both experiments, bacterial translocation was promoted to a similar extent by the ALA-GLN and ALA TPN formulas compared with the rat food groups. Bacterial overgrowth in the cecum and intestinal atrophy, quantitated by the mucosal protein content, did not differ between ALA-GLN and ALA groups. The nitrogen balances of the three groups showed similar values in the second experiment. The secretory immunoglobulin A was measured in washings of the jejunum and ileum (soluble fraction) and in the homogenates of the gut mucosa (insoluble fraction). The secretory immunoglobulin A values of both fractions showed no difference between the ALA and ALA-GLN groups, irrespective of whether they were normalized for gut segment length or corrected for mucosal protein content. In conclusion from these results, the supplementation of TPN with glutamine does not seem to improve gut barrier function or mucosal immunity in unstressed rats.

Alanine↗
PubMed1994

Early impairment of gut mucosal immunity in HIV-1-infected children.

This study was performed in 27 HIV-1+ children to characterize the IgA hyperglobulinaemia observed in the serum during the course of HIV-1 infection. By contrast with serum IgG, which increased very early, IgA elevation was related to the decrease of CD4+ cell percentage. It was demonstrated that IgA1 subclass increased selectively. Secretory IgA (SIgA) and IgA and IgG activity to gliadin, bovine serum albumin (BSA) and at a lower level to casein could be detected in the serum at the early stages of HIV infection, but SIgA levels and IgA activity to gliadin further increased during the course of immunodeficiency. By contrast, IgA and IgG activity to tetanus toxoid did not change. These data demonstrate that the hyper IgA, closely related to the degree of immunodeficiency, could be due in part to a disturbance of the gut mucosal immune system. Moreover, impaired intestinal immunity seems to appear very early, and to progress during the course of paediatric HIV-1 infection.

CD4-Positive T-Lymphocytes↗
PubMed1993

Apathogenic, intestinal, segmented, filamentous bacteria stimulate the mucosal immune system of mice.

Segmented filamentous bacteria (SFBs) are apathogenic autochthonous bacteria in the murine small intestine that preferentially attach to Peyer's patch epithelium. SFBs have never been cultured in vitro. We have studied the effects of SFBs on the immune system of the host. Mice monoassociated with SFBs were compared with germ-free mice and with mice without SFBs but with a specific-pathogen-free (SPF) gut flora. SFBs versus no microbial flora raised the number of lymphoid cells in the lamina propria of the ileal and cecal mucosa, raised the number of immunoglobulin A (IgA)-secreting cells in the intestinal mucosa, produced elevated IgA titers in serum and intestinal secretions, and enhanced the concanavalin A-induced proliferative responses of mesenteric lymph node cells. The SPF flora had effects similar to but less pronounced than those mediated by SFBs. The results indicate that SFBs stimulate the mucosal immune system to a greater extent than do other autochthonous gut bacteria.

Animals↗
PubMed1992

Mucosal immune dysfunction associated with alcoholic IgA nephropathy.

We investigated the hypothesis that alcohol-induced changes of the immune system result in IgA nephropathy (IAN). Wistar rats were infused with liquid diet containing alcohol: "alcoholics." Control rats received an isocaloric diet with glucose instead of alcohol. IAN was diagnosed by mesangial IgA deposition. When compared to controls, serum IgA in alcoholic rats with IAN had a fourfold increase and a twofold increase in alcoholics without IAN. The intestinal lamina propria showed overall lymphocyte depletion in alcoholic rats. The decrease was not uniform for all the lymphocyte subgroups: it resulted in a relative increase in IgA-B cells in alcoholic rats with IAN but not in alcoholic rats without IAN. No significant differences were observed between alcoholic and control rats in the percentages of spleen lymphocyte subtypes. We suggest that dysfunction of the mucosal immune system may be related to the induction of IAN in chronic alcohol consumption.

Alcoholism↗
PubMed2003

Mucosal immune response to Tropheryma whipplei.

Whipple's disease is a rare infectious disease caused by the ubiquitously occurring Tropheryma whipplei in predisposed persons. Genetic or acquired defects in the mucosal and peripheral immune system become apparent as diminished Th1 immune functions with decreased production of IL-12 and IFN-gamma accompanied by an increased secretion of IL-4. These defects may enable T. whipplei to survive and replicate. The recently established cultivation of the bacterium in HEL cells and the isolation from infected intestinal biopsies enable a multitude of experimental possibilities which may lead to an improved diagnosis as well as understanding of the etiology and pathogenesis of Whipple's disease.

Actinomycetales↗
PubMed1992

Boosted mucosal immune responsiveness in the rat intestine by actively transported hexose.

Anaphylaxis-mediated intestinal fluid secretion was measured in Trichinella spiralis- or ovalbumin-immunized rats challenged intraduodenally with T. spiralis somatic antigen (1 mg protein/0.5 mL saline) or ovalbumin (1 mg/0.5 mL saline), respectively. Intestinal fluid volume was measured 30 minutes after challenge as an index of net secretion. Challenge with the antigenic bolus containing 40 mmol/L D-glucose induced twice the fluid secretion as that induced by either antigen alone. L-Glucose was an ineffective substitute for D-glucose. The enhancement of secretion by D-glucose was dependent on prior immunologic sensitization, was diminished in the presence of phlorizin, and was mimicked by beta-methyl glucoside. Results indicate that the active transport of D-glucose augments the antigen-mediated fluid secretion, possibly by enhancing permeation of the intestinal epithelium to antigen, thereby providing greater access to the mucosal immune system.

Anaphylaxis↗
PubMed1992

Immunosenescence and mucosal immunity: significant effects of old age on secretory IgA concentrations and intraepithelial lymphocyte counts.

Concentrations of immunoglobulins (Ig) and levels of isotype specific antibodies to three dietary antigens in serum, pure parotid saliva, and in intestinal secretions obtained by whole gut lavage from groups of healthy elderly subjects (aged greater than 70 years) and of younger adult controls (aged 25-50 years) were measured. In addition, counts of lamina propria and intra-epithelial lymphoid cells were performed in histologically normal jejunal biopsy specimens from elderly and younger subjects. Elderly subjects had significantly higher concentrations of serum and salivary IgA and of salivary IgM (both, p less than 0.01), and of salivary IgA antibodies than did the younger subjects, but the amount of immunoglobulin and antibody in whole gut lavage fluid was similar in the two age groups. Jejunal biopsy specimen cell counts showed higher IgA plasma cell counts and lower intraepithelial lymphocyte counts in the elderly group (p less than 0.01), with similar counts of IgM and IgG plasma cells, eosinophils, and mast cells in the two groups. There is evidence of significant effects of old age on the mucosal immune system.

Adult↗
PubMed2004

Regional differences in the early mucosal immune response induced by primary inoculation of mice with respiratory syncytial virus.

Respiratory syncytial virus (RSV) is the most important cause of respiratory tract infection in infants. Little is known about the characteristics of critical immunologic inductive sites within respiratory-associated lymphoid tissues (RALT) upon RSV infection. We examined the kinetics and characteristics of early mucosal RSV-specific immune responses after primary inoculation of mice. We found that the initial production of virus-specific antibodies was restricted to the organized lymphoid tissues of RALT, such as nasal-associated lymphoid tissue (NALT), cervical and bronchial lymph nodes (CLN and BLN). In addition, virus-specific IgM was produced by B cells resident in CLN and BLN, but not NALT, of mice. Finally, we observed regional differences in the pattern of RSV-specific antibodies produced by RALT; B cells within NALT and CLN produced equivalent quantities of virus-specific IgG2a and IgG2b. However, an IgG2a response predominated in BLN. Together these data demonstrate regional differences in the early mucosal immune response to RSV. Further understanding of these differences may assist the development of RSV vaccines.

Animals↗
PubMed1994

A subunit gIV vaccine, produced by transfected mammalian cells in culture, induces mucosal immunity against bovine herpesvirus-1 in cattle.

A truncated version of bovine herpesvirus-1 (BHV-1) glycoprotein IV (tgIV) was produced in a novel, non-destructive expression system based upon regulation of gene expression by the bovine heat-shock protein 70A (hsp70) gene promoter in Madin Darby bovine kidney (MDBK) cells. In this system, up to 20 micrograms ml-1 of secreted tgIV, which is equivalent to the yield from 4 x 10(6) cells, was produced daily over a period of up to 18 days. Different doses of tgIV were injected intramuscularly into seronegative calves. Virus-neutralizing antibodies were induced by all doses of tgIV, both in the serum and in the nasal superficial mucosa. However, the low dose (2.3 micrograms) induced significantly (p < 0.05) lower antibody titres than the medium (7 micrograms) and high (21 micrograms) doses. The medium and high doses of tgIV conferred protection from BHV-1 infection, as demonstrated by a significant (p < 0.05) reduction in clinical signs of respiratory disease and virus shedding in the nasal secretions postchallenge. However, the 2.3 micrograms group, although partially protected, was not significantly (p > 0.05) different from the placebo group. This study demonstrated the potential of an intramuscularly administered tgIV subunit vaccine to induce mucosal immunity to BHV-1 using an economic protein production system and an acceptable vaccine formulation. In addition, a strong correlation was observed between neutralizing antibodies in the serum and nasal superficial mucosa, virus shedding and clinical disease. Thus, serum neutralizing antibody levels in tgIV-immunized animals may be a good prognosticator of protection from BHV-1 infection and disease.

Animals↗
PubMed2026

Whole cell inactivated poly-bacterial preparation MV130 effect on nasal mucosal immunity and experimental human pneumococcal carriage: double-blind randomised controlled trial with controlled human infection model.

BACKGROUND: Bacterial mucosal immunotherapy has shown protection of children and adults from both viral and bacterial respiratory infections, offering the potential to reduce antimicrobial use, and hence also control antimicrobial resistance (AMR). Pneumococcal carriage of vaccine type Streptococcus pneumoniae remains high in Malawi despite infant conjugate vaccination and AMR is increasing. We compared nasal inflammation following sublingual bacterial immunotherapy including S. pneumoniae (MV130, Inmunotek, Spain) or placebo and determined the effect in an experimental human pneumococcal carriage model. METHODS: A double-blind, randomised, placebo-controlled trial in healthy adult volunteers was conducted at Queen Elizabeth Central Hospital in Blantyre, Malawi. Participants were randomly allocated to receive MV130 or placebo sublingually once daily for 42 days. Mucosal inflammation (neutrophil to T cell ratio, NTR) was measured in nasal micro-biopsies. Post-treatment, participants were challenged with 160,000 CFU/naris S. pneumoniae 6B (Spn6b). Experimental pneumococcal carriage rates post inoculation were compared between the two arms. All participants completing the study were included in the analysis. Prospective trial registration: PACTR202403820001276. FINDINGS: 107 participants were enrolled and randomised to MV130/placebo between May and December 2024. There were no serious adverse events, complete compliance was good (72%) and all adverse events were mild. 96 participants (53 male, 43 female) completed the study with 52 participants randomised to MV130 and 44 to placebo. There was no difference in mucosal inflammation (neutrophil to T cell ratio) at day 14 of the intervention MV130 NTR median = 0.737 (IQR 0.294, 2.059) and placebo NTR = 0.831 (IQR 0.450, 2.073), p = 0.64. Secondary analyses showed a rise in mucosal neutrophils after MV130 treatment and after experimental pneumococcal inoculation. There was no difference in nasal or serum anti-pneumococcal immunoglobulin or in experimental pneumococcal carriage proportion between MV130 (12/52, 23%) and placebo (10/44, 23%) groups (unadjusted risk ratio 1.02 (CI 0.49-2.12) p = 1.0). INTERPRETATION: MV130 induced non-specific mild neutrophil inflammation of the nasal mucosa but had no protective effect against experimental human pneumococcal carriage. FUNDING: Wellcome Trust.

Humans↗
PubMed2004

Intense training: mucosal immunity and incidence of respiratory infections.

This investigation examined the impact of a multistressor situation on salivary immunoglobulin A (sIgA) levels, and incidence of upper respiratory tract infection (URTI) during the French commando training (3 weeks of training followed by a 5-day combat course). For the URTI, the types of symptoms were classified according to the anatomical location of the infection. Saliva samples were collected (8 a.m.) from 21 males [21 (2) years] before entry into the commando training, the morning following the 3 weeks of training, after the 5-day combat course, and after 1 week of recovery. sIgA, protein and cortisol concentrations were measured. Symptoms of URTI were recorded during the study from health logs and medical examinations. After the 3 weeks of training, the sIgA concentration was not changed, although it was reduced after the 5-day course [from 120 (14) mg l(-1) to 71 (9) mg l(-1), P<0.01]. It returned to pre-training levels within a week of recovery. The incidence of URTI increased during the trial (chi(2)=53.48; P<0.01), but was not related to sIgA. Among the 30 episodes of URTI reported, there were 12 rhino-pharyngitis, 6 bronchitis, 5 tonsillitis, 4 sinusitis and 3 otitis. Cortisol levels were raised after the 3-week training (P<0.01), dropping below baseline after the combat course (P<0.01). Stressful situations have an adverse effect on mucosal immunity and incidence of URTI. However, the relationship between sIgA and illness remained unclear. The large proportion of rhino-pharyngitis indicated that the nasopharyngeal cavity is at a higher risk of infection.

Adaptation, Physiological↗