Immunization with mycobacterial antigens: a role for innate immunity in antigen presentation

• We have found that toll-like receptor (TLR) 2 was important in the control of mycobacterial infection in the lungs. However, it is unclear how the TLR2-mediated innate immunity contributes to the development of acquired immune responses upon immunization with mycobacterial antigens. In the present study, we addressed this issue by immunizing TLR2 knockout (TLR2-/-) and wild-type (WT) mice with mycobacterial 19kDa (TLR2 ligand) or Ag85A (non-TLR2 ligand) antigens. We compared both humoral and cellular immune responses in the two mouse strains. Interferon gamma (IFN-g) responses were measured in the culture supernatants after in vitro restimulation of spleen cells with antigen alone, antigen-pulsed bone marrow derived macrophages (BMMAg) or BCG-infected BMM (BMMBCG). We found that the magnitude of antigen-specific antibody responses in serum was comparable in the two mouse strains. With regard to the two antigens, immunization with 19kDa induces more Th1 type immune responses compared to the immunization with Ag85A. We observed differences in the response of the two strains upon restimulation with antigen alone or with BMMAg regarding 19kDa. Recall IFN-g responses to 19kDa were significantly lower in the TLR2-/- mice compared to the WT mice. Interestingly, IFN-g responses to BMMBCG were similar in both strains probably due to the fact that BCG targets other cell surface molecules. The expression of CD86 in the BMMBCG was found to be TLR2-independent whereas in the BMMAg it was TLR2-dependent. Altogether, results from this study indicate that specific immune responses could be generated in the absence of TLR2 regardless of the characteristics of the antigens (TLR2 dependent or independent) used for immunization. We discuss the relevance of innate immunity for the induction of acquired immune responses.

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