ovalbumin and Tuberculosis--Pulmonary

Most microbes invading through mucosal surfaces cause disease and therefore strategies to induce mucosal immune responses are strongly needed. Vitamin A metabolites, such as retinoic acid (RA), play crucial roles in programming T and B cells to home to mucosal compartments, therefore we evaluated the capacity of RA to elicit mucosal immune responses against tuberculosis (TB) after parenteral vaccination. We found that mice immunized through subcutaneous injections with the TB subunit vaccine (CAF01+H56) in presence of RA show enhanced mucosal H56-specific IgA responses and enhanced Ag-specific CD4

Topics: Allergens; Animals; Antibodies, Bacterial; Antibody-Producing Cells; CD4-Positive T-Lymphocytes; Cytokines; Female; Immunity, Mucosal; Immunoglobulin A; Immunoglobulin G; Lung; Lymphocytes; Mice; Mycobacterium tuberculosis; Ovalbumin; Tretinoin; Tuberculosis Vaccines; Tuberculosis, Pulmonary; Vaccination; Vaccines, Subunit

Individuals infected with mycobacteria are likely to experience episodes of concurrent infections with unrelated respiratory pathogens, including the seasonal or pandemic circulating influenza A virus strains. We analyzed the impact of influenza A virus and mycobacterial respiratory coinfection on the development of CD8 T cell responses to each pathogen. Coinfected mice exhibited reduced frequency and numbers of CD8 T cells specific to Mycobacterium bovis bacille Calmette-Guérin (BCG) in the lungs, and the IFN-γ CD8 T cell response to BCG-encoded OVA was decreased in the lungs of coinfected mice, when compared with mice infected with BCG alone. Moreover, after 2 wk of infection, mice coinfected with both pathogens showed a significant increase in the number of mycobacteria present in the lung compared with mice infected with BCG only. Following adoptive transfer into coinfected mice, transgenic CD8 T cells specific for OVA(257-264) failed to proliferate as extensively in the mediastinal lymph nodes as in mice infected only with BCG-OVA. Also noted was a reduction in the proliferation of BCG-specific CD4 transgenic T cells in mice coinfected with influenza compared with mice infected with BCG alone. Furthermore, phenotypic analysis of CD11c(+) dendritic cells from mediastinal lymph nodes of the infected mice showed that coinfection was associated with decreased surface expression of MHC class II and class I. Thus, concurrent pulmonary infection with influenza A virus is associated with decreased MHC expression on dendritic cells, reduced activation of BCG-specific CD4 and CD8 T cells, and impaired clearance of mycobacteria.

Topics: Animals; Cells, Cultured; Coculture Techniques; Female; HEK293 Cells; Humans; Influenza A virus; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mycobacterium bovis; Orthomyxoviridae Infections; Ovalbumin; T-Lymphocyte Subsets; Tuberculosis, Pulmonary

The inverse correlation of mycobacterial infection with asthma prevalence and the inhibitory effects of vaccination with Bacille Calmette-Guérin (BCG) on airway hyperreactivity in asthma models suggest modulation of dendritic cell (DC) and T cell functions by mycobacterial compounds.. To delineate these immunological effects, the immunogenicity of BCG Copenhagen, BCG Chicago and BCG Pasteur was compared in a mouse model. Bone marrow-derived dendritic cells (BMDCs) from BALB/c mice were stimulated with ovalbumin (OVA) with or without BCG. BMDCs were phenotypically characterized by flow cytometry, and we used ELISA to measure the cytokine production of BMDCs as well as of co-cultivated allergen-specific T cells in response to OVA-pulsed. Immunomodulatory effects of BCG were studied in a model of allergic airway inflammation by adoptive transfer of allergen-pulsed BMDCs.. Immunomodulation with BCG induced production of IL-10 and IL-12 by BMDCs. Co-cultured allergen-specific T cells produced less IL-5, IL-13 and IFN-gamma but more IL-10. Also the number of FoxP3(+) regulatory T cells was enhanced. Strongest effects were seen with BCG Chicago and BCG Pasteur. In vivo, administration of BCG modulated OVA-pulsed BMDCs then reduced eosinophilic airway inflammation but enhanced infiltration with granulocytes. Airway hyperreactivity and mucus production were reduced and more FoxP3(+) T cells were observed.. BCG-induced suppression of Th2-type allergic airway inflammation was associated with enhancement of regulatory T cell function but also of Th1-associated neutrophilic airway inflammation. These findings raise concerns regarding the safety profile of BCG as a potential tool for prevention and therapy of allergic airway disease.

Topics: Allergens; Animals; BCG Vaccine; Coculture Techniques; Cytokines; Dendritic Cells; Female; Mice; Mice, Inbred BALB C; Mice, Transgenic; Neutrophil Infiltration; Ovalbumin; Receptors, Antigen, T-Cell; Respiratory Hypersensitivity; T-Lymphocytes, Regulatory; Th1 Cells; Th2 Cells; Tuberculosis, Pulmonary

During pulmonary mycobacterial infection, there is increased trafficking of dendritic cells from the lungs to the draining lymph nodes. We hypothesized that ongoing mycobacterial infection would modulate recruitment and activation of antigen-specific naive CD4+ T cells after airway antigen challenge. BALB/c mice were infected by aerosol with Mycobacterium bovis BCG. At peak bacterial burden in the lungs (4 to 6 weeks postinfection), carboxy-fluorescein diacetate succinimidyl ester-labeled naive ovalbumin-specific DO11.10 T cells were adoptively transferred into infected and uninfected mice. Recipient mice were challenged intranasally with soluble ovalbumin (OVA), and OVA-specific T-cell responses were measured in the lungs, draining mediastinal lymph nodes (MLN), and spleens. OVA challenge resulted in increased activation and proliferation of OVA-specific T cells in the draining MLN of both infected and uninfected mice. However, only BCG-infected mice had prominent OVA-specific T-cell activation, proliferation, and Th1 differentiation in the lungs. BCG infection caused greater distribution of airway OVA to pulmonary dendritic cells and enhanced presentation of OVA peptide by lung CD11c+ cells. Together, these data suggest that an existing pulmonary mycobacterial infection alters the phenotype of lung dendritic cells so that they can activate antigen-specific naive CD4+ T cells in the lungs in response to airway antigen challenge.

Topics: Adoptive Transfer; Animals; Antigens; CD11c Antigen; CD4-Positive T-Lymphocytes; Dendritic Cells; Female; Lung; Lymph Nodes; Lymphocyte Activation; Mediastinum; Mice; Mice, Inbred BALB C; Mycobacterium bovis; Ovalbumin; Th1 Cells; Tuberculosis, Pulmonary

Bronchial-alveolar eosinophilic inflammation is among the characteristic pathological changes in asthma, which has been shown to be correlated with type 2 cytokine and chemokine production. Exogenous IL-12 has been found to be inhibitory for pulmonary eosinophilia in reported studies. Using a murine asthma-like model induced by OVA, we found in the present study that IL-12 gene knockout (KO) mice showed substantially reduced airway recruitment of eosinophils compared with wild-type control mice following OVA sensitization/challenge, although the levels of circulating eosinophils were comparable in these two groups of mice. Cytokine analysis showed Ag-driven Th1 (IFN-gamma) and Th2 (IL-4, IL-5, IL-10, and IL-13) cytokine production by CD4 T cells from local draining lymph nodes and spleen. Similarly, local eotaxin production was comparable in wild-type and IL-12 KO mice. In contrast, immunohistochemical analysis showed that the expression of VCAM-1 on the lung endothelium of IL-12 KO mice was dramatically less than that in wild-type mice. Furthermore, administration of rIL-12 at the stage of sensitization and challenge with OVA restored airway eosinophilia and VCAM-1 expression in IL-12 KO mice. The results suggest that endogenous IL-12 contributes to the recruitment of eosinophils into airways observed in asthma, possibly via enhancement of the expression of VCAM-1 on local vascular endothelial cells.

Topics: Administration, Intranasal; Animals; Asthma; Bronchi; Cytokines; Disease Models, Animal; Down-Regulation; Endothelium, Vascular; Female; Immunoglobulin E; Immunoglobulin G; Injections, Intraperitoneal; Interleukin-12; Intracellular Fluid; Mice; Mice, Inbred C57BL; Mice, Knockout; Mycobacterium bovis; Ovalbumin; Pulmonary Eosinophilia; Recombinant Proteins; Th1 Cells; Th2 Cells; Tuberculosis, Pulmonary; Vascular Cell Adhesion Molecule-1

Topics: Animals; Antigens, Bacterial; Cattle; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; gamma-Globulins; Glycolipids; Goats; Humans; Leprosy; Monosaccharides; Mycobacterium leprae; Ovalbumin; Serum Albumin, Bovine; Tuberculosis, Pulmonary

A water-soluble mycobacterial glycopeptide was obtained in large quantities from the culture supernatant fluid of M. tuberculosis strain DT. This glycopeptide was strongly adjuvant-active when injected, in a water-in-oil emulsion contianing ovalbumin, into guinea-pigs. In addition, it was devoid of cord factor toxicity in mice, polyarthritogenic activity in rats and cavity stimulating activity in rabbit lungs.

Topics: Adjuvants, Immunologic; Animals; Arthritis; Cord Factors; Cornea; Glycopeptides; Glycoproteins; Guinea Pigs; Hypersensitivity, Delayed; Immunoglobulin G; Mycobacterium tuberculosis; Ovalbumin; Precipitin Tests; Rabbits; Rats; Rats, Inbred Lew; Skin Tests; Solubility; Tuberculosis, Pulmonary