Polymeric Ig receptor knockout mice are more susceptible to mycobacteria infection in the respiratory tract
2006 (English)In: International Immunology, ISSN 0953-8178, E-ISSN 1460-2377, Vol. 18, no 5, 807-816 p.Article in journal (Refereed) Published
It is generally accepted that cellular, and not humoral immunity, plays the crucial role in defense against intracellular bacteria. However, accumulating data indicate the importance of humoral immunity for the defense against a number of intracellular bacteria, including mycobacteria. We have investigated the role of secretory IgA, the main isotype found in mucosal tissues, in protection against mycobacterial infection, using polymeric IgR (pIgR)-deficient mice. Characterization of the humoral response induced after intra-nasal immunizations with the mycobacterial antigen PstS-1 revealed a loss of antigen-specific IgA response in saliva from the knockout mice. IgA level in the bronchoalveolar lavage of knockout mice was similar to wild-type level, although the IgA antibodies must have reached the lumen by other means than pIgR-mediated transport. Infection with Mycobacterium bovis bacillus Calmette–Guérin (BCG) demonstrated that the immunized pIgR−/− mice were more susceptible to BCG infection than immunized wild-type mice, based on higher bacterial loads in the lungs. This was accompanied by a reduced production of both IFN-γ and tumor necrosis factor-alpha (TNF-α) in the lungs. Additionally, the pIgR−/− mice displayed reduced natural resistance to mycobacterial infection proved by significantly higher bacterial growth in their lungs compared with wild-type mice after infection with virulent Mycobacterium tuberculosis. The knockout mice appeared to have a delayed mycobacteria-induced immune response with reduced expression of protective mediators, such as IFN-γ, TNF-α, inducible nitric oxide synthase and regulated upon activation normal T cell sequence, during early infection. Collectively, our results show that actively secreted IgA plays a role in protection against mycobacterial infections in the respiratory tract, by blocking entrance of bacilli into the lungs, in addition to modulation of the mycobacteria-induced pro-inflammatory response.
Place, publisher, year, edition, pages
oxford university press , 2006. Vol. 18, no 5, 807-816 p.
mucosal immunity mycobacteria pIgR secretory IgA
Immunology in the medical area
IdentifiersURN: urn:nbn:se:su:diva-23926DOI: 10.1093/intimm/dxl017OAI: oai:DiVA.org:su-23926DiVA: diva2:195380
Part of urn:nbn:se:su:diva-5522005-06-232005-06-232010-11-02Bibliographically approved