DIFFERENTIAL INVOLVEMENT OF PRRS IN THE EXPANSION OF M. TUBERCULOSIS- INDUCED TH17 CELLS FROM PATIENTS WITH MULTIDRUG-RESISTANT TUBERCULOSIS.

BASILE JI; SABIO Y GARCÍA CA; RITACCO V; GARCÍA A; CUFFRÉ M; GONZÁLEZ MONTANER P; DE CASADO GC; PALMERO D; SASIAIN MC; DE LA BARRERA S

Lima

Congreso; Inmuno Perú 2012; 2012

Asociación latinoamericana de Inmunología

We demonstrated that the most prevalent multidrug-resistant (MDR) strains of M. tuberculosis from Argentina, namely M and Ra, induced strong Th17 responses in MDR-TB patients through the expansion of IL- 17+IFNgneg T cells. In contrast, a weak Th17 response was observed in PPD+ healthy donors (N) being IL-17+IFNg+ T cells the main Th17 subset. In this work we assessed the involvement of PRRs belonging to TLR, C-type like lectins and CD14 on the differential expansion of both Mtb-induced Th17 subsets. PMBC from 5 N and 5 MDR-TB were cultured with M, Ra, or H37Rv for 48 hr in the presence or absence of neutralizing MoAbs against TLR-2, TLR-4, MR, Dectin-1 (Dec1) and CD14. IL-17 and IFNg expression were evaluated by flow cytometry and results are expressed as percentage of IL-17+IFNgneg/+ cells within the CD4+ T subset. Results: a) N: percentage of IL-17+IFNgneg and of IL-17+IFNg+ cells were reduced by anti-Dec1 being this effect independent on the strain. b) MDR-TB: anti-Dec1 decreased percentage of IL-17+IFNgneg and of IL-17+IFNg+ cells regardless the strain. Interestingly, blockade of TLR2 or TLR4 only reduced the % IL-17+IFNgneg. Conclusions: These preliminary results suggest that regardless the strain, Dec1 is the main PPR involved in the overall Mtb-induced Th17 response. Besides, in MDR-TB, TLR2 and TLR4 could amplify and direct this response towards an IL-17+IFNg- phenotype.