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At least 289 records · Page 16Linked to original sources
PubMed2006

Mucosal immunity to asymptomatic Entamoeba histolytica and Entamoeba dispar infection is associated with a peak intestinal anti-lectin immunoglobulin A antibody response.

We monitored 93 subjects cured of amebic liver abscess (ALA) and 963 close associate controls in Durban, South Africa, and determined by enzyme-linked immunosorbent assay that the intestinal immunoglobulin A (IgA) antibody response to the Entamoeba histolytica galactose-inhibitable adherence lectin is most accurately represented by a complex pattern of transitory peaks. One or more intestinal anti-lectin IgA antibody peaks occurred in 85.9% of ALA subjects over 36 months compared to 41.6% of controls (P < 0.0001). ALA subjects exhibited a greater number of anti-lectin IgA antibody peaks (P < 0.0001) than controls. In addition, their peak optical density values were higher (peak numbers 1 to 3, P < 0.003), peaks were of longer duration (for peaks 1 and 2, P </= 0.0054), and there was a shorter time interval between peaks (between 1 and 2 or 2 and 3, P </= 0.0106) than observed for control subjects. A prior E. histolytica infection was associated with the occurrence of an anti-lectin IgA antibody peak (79.1%, P < 0.0001) more so than for Entamoeba dispar infection (57.2%, P < 0.001). The annual number of anti-lectin IgA antibody peaks in ALA subjects was 0.71 per year, compared to just 0.22 in controls (P<0.0001), indicating a higher rate of exposure to the parasite than previously appreciated. Anti-lectin IgA antibody peaks were of higher amplitude following a E. histolytica infection compared to E. dispar (P = 0.01) and, for either, were of greater height in ALA subjects than controls (P < 0.01). ALA subjects demonstrated greater clearance of amebic infection after an anti-lectin IgA antibody peak compared to controls, and only 14.3% remained with a positive culture after the peak, compared to 38.9% in controls (P = 0.035). In summary, this prospective controlled longitudinal study elucidated the dynamic nature of the human intestinal IgA antibody response to E. histolytica and E. dispar infection and revealed that ALA subjects exhibit heightened intestinal anti-lectin IgA antibody peaks that are associated with clearance of E. histolytica and E. dispar infection.

Adult↗
PubMed2001

Analysis of chicken mucosal immune response to Eimeria tenella and Eimeria maxima infection by quantitative reverse transcription-PCR.

The recent cloning of chicken genes coding for interleukins, chemokines, and other proteins involved in immune regulation and inflammation allowed us to analyze their expression during infection with Eimeria. The expression levels of different genes in jejunal and cecal RNA extracts isolated from uninfected chickens and chickens infected with Eimeria maxima or E. tenella were measured using a precise quantitative reverse transcription-PCR technique. Seven days after E. tenella infection, expression of the proinflammatory cytokine interleukin-1beta (IL-1beta) mRNA was increased 80-fold. Among the chemokines analyzed, the CC chemokines K203 (200-fold) and macrophage inflammatory factor 1beta (MIP-1beta) (80-fold) were strongly upregulated in the infected ceca, but the CXC chemokines IL-8 and K60 were not. However, the CXC chemokines were expressed at very high levels in uninfected cecal extracts. The levels of gamma interferon (IFN-gamma) (300-fold), inducible nitric oxide synthase (iNOS) (200-fold), and myelomonocytic growth factor (MGF) (50-fold) were also highly upregulated during infection with E. tenella, whereas cyclooxygenase 2 showed a more modest (13-fold) increase. The genes upregulated during E. tenella infection were generally also upregulated during E. maxima infection but at a lower magnitude except for those encoding MIP-1beta and MGF. For these two cytokines, no significant change in expression levels was observed after E. maxima infection. CD3+ intraepithelial lymphocytes may participate in the IFN-gamma upregulation observed after infection, since both recruitment and upregulation of the IFN-gamma mRNA level were observed in the infected jejunal mucosa. Moreover, in the chicken macrophage cell line HD-11, CC chemokines, MGF, IL-1beta, and iNOS were inducible by IFN-gamma, suggesting that macrophages may be one of the cell populations involved in the upregulation of these cytokines observed in vivo during infection with Eimeria.

Animals↗
PubMed1998

Mucosal immunity to herpes simplex virus type 2 infection in the mouse vagina is impaired by in vivo depletion of T lymphocytes.

Intravaginal (IVAG) inoculation of wild-type herpes simplex virus type 2 (HSV-2) in mice causes epithelial infection followed by lethal neurological illness, while IVAG inoculation of attenuated HSV-2 causes epithelial infection followed by development of protective immunity against subsequent IVAG challenge with wild-type virus. The role of T cells in this immunity was studied by in vivo depletion of these cells with monoclonal antibodies. Three groups of mice were used for each experiment: nonimmune/challenged mice, immune/challenged mice, and immune depleted mice [immune mice depleted of a T-cell subset(s) shortly before challenge with HSV-2]. Mice were assessed for epithelial infection 24 h after challenge, virus protein in the vaginal lumen 3 days after challenge, and neurological illness 8 to 14 days after challenge. Monoclonal antibodies to CD4, CD8, or Thy-1 markedly reduced T cells in blood, spleen, and vagina, but major histocompatibility complex class II antigens were still partially upregulated in the vaginal epithelium after virus challenge, indicating that virus-specific memory T-cell function was not entirely eliminated from the vagina. Nevertheless, immune mice depleted of CD4+ and CD8+ T cells, Thy-1+ T cells, or CD8+ T cells alone had greater viral infection in the vaginal epithelium than nondepleted immune mice, indicating that T cells contribute to immunity against vaginal HSV-2 infection. All immune depleted mice retained substantial immunity to epithelial infection and were immune to neurological illness, suggesting that other immune mechanisms such as virus-specific antibody may also contribute to immunity.

Animals↗
PubMed2002

Mucosal immunization of rhesus monkeys against respiratory syncytial virus subgroups A and B and human parainfluenza virus type 3 by using a live cDNA-derived vaccine based on a host range-attenuated bovine parainfluenza virus type 3 vector backbone.

Reverse genetics was used to develop a two-component, trivalent live attenuated vaccine against human parainfluenza virus type 3 (HPIV3) and respiratory syncytial virus (RSV) subgroups A and B. The backbone for each of the two components of this vaccine was the attenuated recombinant bovine/human PIV3 (rB/HPIV3), a recombinant BPIV3 in which the bovine HN and F protective antigens are replaced by their HPIV3 counterparts (48). This chimera retains the well-characterized host range attenuation phenotype of BPIV3, which appears to be appropriate for immunization of young infants. The open reading frames (ORFs) for the G and F major protective antigens of RSV subgroup A and B were each placed under the control of PIV3 transcription signals and inserted individually or in homologous pairs as supernumerary genes in the promoter proximal position of rB/HPIV3. The level of replication of rB/HPIV3-RSV chimeric viruses in the respiratory tract of rhesus monkeys was similar to that of their parent virus rB/HPIV3, and each of the chimeras induced a robust immune response to both RSV and HPIV3. RSV-neutralizing antibody titers induced by rB/HPIV3-RSV chimeric viruses were equivalent to those induced by infection with wild-type RSV, and HPIV3-specific antibody responses were similar to, or slightly less than, after infection with the rB/HPIV3 vector itself. This study describes a novel vaccine strategy against RSV in which vaccine viruses with a common attenuated backbone, specifically rB/HPIV3 derivatives expressing the G and/or F major protective antigens of RSV subgroup A and of RSV subgroup B, are used to immunize by the intranasal route against RSV and HPIV3, which are the first and second most important viral agents of pediatric respiratory tract disease worldwide.

Animals↗
PubMed1998

Current concepts in mucosal immunity. II. One size fits all: nonclassical MHC molecules fulfill multiple roles in epithelial cell function.

The human major histocompatibility complex (MHC) on chromosome 6 encodes three classical class I genes: human leukocyte antigen-A (HLA-A), HLA-B, and HLA-C. These polymorphic genes encode a 43- to 45-kDa cell surface glycoprotein that, in association with the 12-kDa beta 2-microglobulin molecule, functions in the presentation of nine amino acid peptides to the T cell receptor of CD8-bearing T lymphocytes and killer inhibitory receptors on natural killer cells. In addition to these ubiquitously expressed polymorphic proteins, the human genome also encodes a number of nonclassical MHC class I-like, or class Ib, genes that in general encode nonpolymorphic molecules involved in a variety of specific immunologic functions. Many of these genes, including CD1, the neonatal Fc receptor for immunoglobulin G, HLA-G, the MHC class I chain-related gene A, and Hfe, are prominently displayed on epithelial cells, suggesting an important role in epithelial cell biology.

Animals↗
PubMed2003

Effects of physical activity, body fat, and salivary cortisol on mucosal immunity in children.

This study examined relationships among physical activity, body composition, and stress- and immunity-related variables in fifth grade children (10-11 yr) in Southern Ontario. The 29 boys and 32 girls, who participated in the study, performed a 20-m shuttle run for prediction of aerobic fitness. Bioelectrical impedance was used to assess relative body fat. Standardized questionnaires were used to determine physical activity-related variables and frequency of upper respiratory tract infection (URTI). Resting saliva samples were collected and tested for resting cortisol and resting secretory immunoglobulin A (SIgA). Subjects wore a pedometer for 48 h to estimate their average total distance traveled per day. SIgA was significantly correlated with reported URTIs but was not related to salivary cortisol, physical activity, fitness level, or relative body fat. Children who spent more time in sport activities and had higher aerobic fitness reported fewer "sick" days. Children with body fat higher than 25% reported significantly (P < 0.05) more sick days than the rest of the cohort. There were no gender differences in SIgA, URTI frequency, and cortisol levels. The test-retest reproducibility for salivary cortisol was 0.66 (P < 0.01), whereas long-term SIgA reproducibility was nonsignificant for repeated measurements taken after 6 wk. Resting secretory immunity was not strongly related to fitness and physical activity, but there was evidence that reduced physical activity and excess body fat can result in higher URTI incidence.

Adipose Tissue↗
PubMed1999

Topical CTLA4-Ig suppresses ongoing mucosal immune response in presensitized murine model of allergic rhinitis.

Allergic rhinitis is thought to be mediated by CD4+ T cells producing Th2-associated cytokines. Optimal Ag-specific T-cell activation requires the engagement of T-cell receptor with antigen (Ag) in the context of MHC, and the engagement of appropriate costimulatory molecules. One of the most well-characterized costimulatory pathways is the interaction of B7/CD28-CTLA4 molecules. Recent studies have suggested that the costimulatory pathway may influence the development of Th2 immune responses. The objective of this study was the examination of the role of B7/CD28-CTLA4 costimulatory pathway in the pathogenesis of ovalbumin (OVA)-induced immune response in presensitized murine model of allergic rhinitis. Systemically presensitized BALB/c mice significantly developed Ag-induced early phase nasal symptoms, nasal hyperresponsiveness to histamine, nasal eosinophilia, serum levels of OVA- specific IgE and Th2-associated cytokines following repeated topical Ag challenges. Topical administration of CTLA4-Ig during nasal challenges inhibited Ag-induced nasal symptoms and histamine hyperresponsiveness. We also found a significant reduction in nasal lavage eosinophilia and serum levels of OVA-specific IgE. Furthermore, CTLA4-Ig treatment significantly decreased interleukin (IL)-4 content in nasal tissue, while there was no significant change in IL-5 or IFN-gamma levels. These results suggest that B7/CD28-CTLA4 costimulatory pathway mediates the development of ongoing Th2 immune responses and plays a major role in regulating allergic disease, such as allergic rhinitis.

Abatacept↗
PubMed2025

Fecal microbiota transplantation promotes type 2 mucosal immune responses with colonic epithelium proliferation in patients with recurrent Clostridioides difficile.

BACKGROUNDFecal microbiota transplantation (FMT) is the most effective therapy for recurrent Clostridioides difficile infection (rCDI), yet its mechanism of action remains poorly understood.METHODSWe report the results of a clinical trial of patients undergoing FMT therapy for rCDI (n = 16), which analyzed colon biopsies, plasma, PBMCs, and stool at the time of FMT and 2-month follow-up. Plasma and colon biopsy samples were also collected from healthy controls for comparison with patients with rCDI. Microbiome composition, colonic gene expression, and immune changes were evaluated through high-throughput sequencing and immunoprofiling via flow cytometry.RESULTSNo patients experienced recurrence at follow-up. FMT significantly altered the intestinal microbiome but had no significant impact on the systemic immune system. In contrast, FMT promoted broad changes in colonic transcriptional profiles compared with both pre-FMT and healthy control biopsies, inhibiting genes associated with proinflammatory signaling and upregulating type 2 immunity and proliferative pathways (Myc and mTORC1). FMT increased expression of IL-33 and the type 2 immune EGFR family ligand amphiregulin, potentially explaining upregulation of Myc and mTORC1 pathways. Spatial transcriptomics demonstrated that these changes were localized to the colonic epithelium. Comparison of transcriptional profiles with available single-cell gene sets determined that post-FMT biopsies were enriched in signatures associated with proliferative cell types while repressing signatures of differentiated colonocytes.CONCLUSIONWe conclude that FMT promotes proliferation of the colonic epithelium in patients with rCDI, which may drive regeneration and protect against subsequent CDI.TRIAL REGISTRATIONClinicaltrials.gov NCT02797288.FUNDINGThis work was funded by grants from the NIH.

Adult↗
PubMed2005

Induction of anti-chlamydial mucosal immunity by transcutaneous immunization is enhanced by topical application of GM-CSF.

Transcutaneous immunization (TCI) involves the direct application of antigen plus adjuvant to skin, taking advantage of the large numbers of Langerhans cells and other resident skin dendritic cells, that process antigen then migrate to draining lymph nodes where immune responses are initiated. We have used this form of immunization to protect mice against genital tract and respiratory tract chlamydial infection. Protection was associated with local antibody responses in the vagina, uterus and lung as well as strong Th1 responses in the lymph nodes draining the reproductive tract and lungs respectively. In this study we show that topical application of GM-CSF to skin enhances the numbers and activation status of epidermal dendritic cells. Topical application of GM-CSF also increased the immune responses elicited by TCI. GM-CSF supplementation greatly increased cytokine (IFNgamma and IL-4) gene expression in lymph node and splenic cells compared to cells from animals immunized without GM-CSF. IgG responses in serum, uterine lavage and bronchoalveolar lavage and IgA responses in vaginal lavage were also increased by topical application of GM-CSF. The studies show that TCI induces protection against genital and respiratory tract chlamydial infections and that topical application of cytokines such as GM-CSF can enhance TCI-induced antibody and cell-mediated immunity.

Administration, Cutaneous↗
PubMed1998

In vivo anti-influenza virus activity of Kampo (Japanese herbal) medicine "sho-seiryu-to"--stimulation of mucosal immune system and effect on allergic pulmonary inflammation model mice.

When BALB/c mice were treated with a Kampo (Japanese herbal) medicine "Sho-seiryu-to (SST)" (1 g/kg, 10 times) orally from 7 days before to 5 days after the infection and infected with mouse-adapted influenza virus A/PR/8/34 by nasal-site restricted infection, SST caused increment of the influenza virus hemagglutinin-specific IgA antibody secreting cells in nasal lymphocyte but not in Peyer's patch lymphocyte at 6 days after infection in comparison with water-treated mice. Oral administration of SST also augmented IL-2 receptor beta chain+ (activated) T-cell in Peyer's patch lymphocyte, but not in the nasal lymphocyte. We previously reported that SST showed potent anti-influenza virus activity through augmentation of the antiviral IgA antibody titer in the nasal and broncho-alveolar cavities of the mice (T. Nagai and H. Yamada, 1994, Int. J. Immunopharmacol. 16, 605-613). These results suggest that oral administration of SST shows anti-influenza virus activity in the nasal cavity by activation of T-cell in Peyer's patch lymphocyte and stimulation of production of anti-influenza virus IgA antibody in nasal lymphocyte. When ovalbumin-sensitized allergic pulmonary inflammation model mice were administered orally with SST (1 g/kg) from 8 days before (11 times) or from 2 h after (4 times) to 4 days after the infection and infected with mouse-adapted influenza virus A/PR/8/34, replications of the virus in the both nasal and broncho-alveolar cavities or only nasal cavity were significantly inhibited at 5 days after infection in comparison with water-treated control by augmenting antiviral IgA antibody, respectively. These results suggest that SST is useful for both prophylaxis and treatment of influenza virus infection on patients with allergic pulmonary inflammation, such as bronchial asthma.

Animals↗
PubMed2000

The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system.

Chemokines play an important role in the migration of leukocytes at sites of inflammation, and some constitutively expressed chemokines may direct lymphocyte trafficking within lymphoid organs and peripheral tissues. Thymus-expressed chemokine (TECK or Ckbeta-15/CCL25), which signals through the chemokine receptor CCR9, is constitutively expressed in the thymus and small intestine but not colon, and chemoattracts a small fraction of PBLs that coexpress the integrin alpha(4)beta(7). Here we show that TECK is expressed in the human small bowel but not colon by endothelial cells and a subset of cells in intestinal crypts and lamina propria. CCR9 is expressed in the majority of freshly isolated small bowel lamina propria mononuclear cells (LPMC) and at significantly higher levels compared with colonic LPMC or PBL. TECK was selectively chemotactic for small bowel but not colonic LPMC in vitro. The TECK-induced chemotaxis was sensitive to pertussis toxin and partially inhibited by Abs to CCR9. TECK attracts predominantly the T cell fraction of small bowel LPMC, whereas sorted CD3(+)CCR9(+) and CD3(+)CCR9(-) lymphocytes produce similar Th1 or Th2 cytokines at the single cell level. Collectively, our data suggest that the selective expression of TECK in the small bowel underlie the homing of CCR9(+) intestinal memory T cells to the small bowel rather than to the colon. This regional specialization implies a segregation of small intestinal from colonic immune responses.

Cell Movement↗
PubMed2002

GM-CSF transgene-based adjuvant allows the establishment of protective mucosal immunity following vaccination with inactivated Chlamydia trachomatis.

Cellular and humoral immune responses induced following murine Chlamydia trachomatis infection confer almost sterile protection against homologous reinfection. On the other hand, immunization with inactivated organism induces little protective immunity in this model system. The underlying mechanism(s) that determines such divergent outcome remains unclear, but elucidating the mechanism will probably be important for chlamydial vaccine development. One of the distinct differences between the two forms of immunization is that chlamydia replication in epithelial cells causes the secretion of a variety of proinflammatory cytokines and chemokines, such as GM-CSF, that may mobilize and mature dendritic cells and thereby enhance the induction of protective immunity. Using a murine model of C. trachomatis mouse pneumonitis lung infection and intrapulmonary adenoviral GM-CSF transfection, we demonstrate that the expression of GM-CSF in the airway compartment significantly enhanced systemic Th1 cellular and local IgA immune responses following immunization with inactivated organisms. Importantly, immunized mice had significantly reduced growth of chlamydia and exhibited less severe pulmonary inflammation following challenge infection. The site of GM-CSF transfection proved important, since mice immunized with inactivated organisms after GM-CSF gene transfer by the i.p. route exhibited little protection against pulmonary challenge, although i.p. immunization generated significant levels of systemic Th1 immune responses. The obvious difference between i.p. and intrapulmonary immunization was the absence of lung IgA responses following i.p. vaccination. In aggregate, the findings demonstrate that the local cytokine environment is critical to the induction of protective immunity following chlamydial vaccination and that GM-CSF may be a useful adjuvant for a chlamydial vaccine.

Adenoviruses, Human↗