Impact of Toll-like receptor 2 deficiency on immune responses to mycobacterial antigens.

RAHMAN MJ; CHUQUIMIA OD; PETURSDOTTIR DH; PERIOLO N; SINGH M; FERNÁNDEZ C

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Año: 2011 vol. 79 p. 4649 - 4656

0019-9567

In the present study, we addressed the question whether the Toll-like receptor 2 (TLR2)-mediated innate immunity can contribute to the development of acquired immune responses. We immunized TLR2-/- and wild-type (WT) mice three times subcutaneously with the mycobacterial antigens 19kDa (TLR2 ligand) or Ag85A (not TLR2 ligand). One week after the last immunization, serum and spleens were collected. To evaluate cellular responses, we measured IFN-g after in vitro re-stimulation of spleen cells with antigen alone, antigen-pulsed bone marrow derived macrophages (BMMAg) or pulmonary macrophages (PuMAg). Antibody responses were comparable in the two mouse strains but we observed differences in the cellular responses. Recall responses to Ag85A were similar in the two strains but responses to 19kDa given alone or presented by BMM or PuM were lower in TLR2-/- compared to WT mice. The largest differences in cellular responses were observed when 19kDa was presented by PuM. To understand this, we analyzed phenotypic and functional differences between BMM and PuM upon stimulation with various ligands. Generally PuM had a lower response to the TLR2 ligand Pam3Cys-Ser-(Lys)4 trihydrochloride and to anti-CD40 than BMM, as measured by cytokine secretion and up-regulation of co-stimulatory molecules. This might provide a partial explanation for the lower capacity of PuM when pulsed with 19kDa, also a TLR2 ligand. Altogether, our results revealed weaknesses in theT cell and APC compartments of the 19kDa immunized TLR2-/- mice but indicated that specific immune responses could be generated in the absence of TLR2 regardless of the characteristics of the antigen used.