International Immunology Advance Access originally published online on March 28, 2006
International Immunology 2006 18(5):807-816; doi:10.1093/intimm/dxl017
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Polymeric IgR knockout mice are more susceptible to mycobacterial infections in the respiratory tract than wild-type mice
1 Department of Immunology, Wenner-Gren Institute, Stockholm University, Svante Arrhenius väg 16, 10691 Stockholm, Sweden
2 Unitat de Tuberculosi Experimental, Fundació Institut Germans Trias i Pujol, Badalona, Catalonia, Spain
3 Department of Oral Medicine and Pathology, Guy's Hospital, London SE1 9RT, UK
4 Gesellschaft für Biotechnologische Forschung mbH, 38124 Braunschweig, Germany
Correspondence to: A. Tjärnlund; E-mail: anna.tjarnlund{at}imun.su.se
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-
and tumor necrosis factor-alpha (TNF-
) 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-, TNF-, 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.
Keywords: mucosal immunity, mycobacteria, pIgR, secretory IgA
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