Role of IgA in the defense against respiratory infections: IgA deficient mice exhibited increased susceptibility to intranasal infection with Mycobacterium bovis BCG

Ariane Rodríguez*, Anna Tjärnlund, Juraj Ivanji, Mahavir Singh, Irene García, Ann Williams, Philip D. Marsh, Marita Troye-Blomberg, Carmen Fernández

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    112 Citations (Scopus)

    Abstract

    IgA is the predominant Ig isotype in mucosal tissue and is believed to be involved in defense against viral and bacterial infections at these sites. Here, we examined the role of IgA in the protection against intranasal (i.n.) infection with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). IgA deficient (IgA-/-) mice and wild type non-targeted littermate (IgA+/+) mice were immunized by i.n. route with the mycobacterium surface antigen PstS-1 formulated with cholera toxin (CT). Our data showed that IgA-/- mice were more susceptible to BCG infection compared to IgA+/+ mice, as revealed by the higher bacterial loads in the lungs and bronchoalveolar lavage (BAL). Analysis of the Ig levels and the antibody responses to PstS-1 showed that IgA-/- mice had no detectable IgA either in the saliva or in the BAL. However, these mice displayed higher levels of total and specific IgM than IgA+/+ mice in both mucosal fluids. More importantly, analysis of the cytokine responses revealed a reduction in the IFN-γ and TNF-α production in the lungs of IgA-/- compared to IgA+/+ mice. Altogether, our results suggest that IgA may play a role in protection against mycobacterial infections in the respiratory tract by blocking the pathogen entrance and/or by modulating the pro-inflammatory responses.

    Original languageEnglish
    Pages (from-to)2565-2572
    Number of pages8
    JournalVaccine
    Volume23
    Issue number20
    DOIs
    Publication statusPublished - 8 Apr 2005

    Bibliographical note

    Funding Information:
    A. Rodriguez and A. Tjärnlund shared first authorship. M. Troye-Blomberg and C. Fernández shared senior authorship. We thank E. Julian, F. Dieli, A. Salerno, J. Tree, R. Reljic and M. Comini for helpful suggestions and discussions. We also are grateful to I. Mbawuike for providing the IgA deficient mice. We thank P.J. Cardona for conducting the challenge experiments with the virulent mycobacteria. This work was financially supported by the European Commission (Fifth Framework Program, Contract QLK2-1999-00367) and by the Hjärt-LungFonden.

    Keywords

    • BCG
    • IgA
    • Mucosal immunity

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