TY - JOUR
T1 - Polymeric IgR knockout mice are more susceptible to mycobacterial infections in the respiratory tract than wild-type mice
AU - Tjärnlund, Anna
AU - Rodríguez, Ariane
AU - Cardona, Pere Joan
AU - Guirado, Evelyn
AU - Ivanyi, Juraj
AU - Singh, Mahavir
AU - Troye-Blomberg, Marita
AU - Fernández, Carmen
N1 - Funding Information:
A. Tjärnlund and A. Rodriguez shared first authorship. We are grateful to P. Marsh and A. Williams for providing the BCG and for insightful comments and suggestions about this work. We thank A. Salerno, F. Dieli, R. Reljic, J. Tree and M. Comini for helpful suggestions and discussions and E. Julián for critical reading of the manuscript. We are also grateful to M. Nanno for providing the pIgR–/– mice. This work was financially supported by the European Commission specific RTD program QLK2-CT-1999-00367 and Hjärt-Lungfonden.
PY - 2006/5/15
Y1 - 2006/5/15
N2 - 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.
AB - 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.
KW - Mucosal immunity
KW - Mycobacteria
KW - plgR
KW - Secretory IgA
UR - http://www.scopus.com/inward/record.url?scp=33646894153&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxl017
DO - 10.1093/intimm/dxl017
M3 - Article
C2 - 16569672
AN - SCOPUS:33646894153
SN - 0953-8178
VL - 18
SP - 807
EP - 816
JO - International Immunology
JF - International Immunology
IS - 5
ER -