C5a anaphylatoxin modulation of immune response induced by local Mtb strains

SABIO Y GARCÍA, CARMEN;; GEFFNER LAURA; YOKOBORI NOEMÍ; GONZALEZ, ALEJANDRA;; ASQUINEYER, YANINA;; LOPEZ BEATRIZ; DE LA BARRERA SILVIA; MARIA DEL CARMEN SASIAIN

Vancouver

Simposio; Keystone Symposia 2011 - Tuberculosis: Immunology, Cell Biology and Novel Vaccination Strategies; 2011

Keystone Symposia

Tuberculosis remains a serious global health problem, aggravated for the appearance of multidrug resistant strains (MDR-TB). In Argentina, the incidence of tuberculosis reported in 2009 was of 26.5 per 100.000 inhabitants; and 4.5% of all cases reported in 2006 were due to MDR strains. Among MDR strains that have been isolated in Buenos Aires and Rosario cities strains M (from Haarlem family) and Ra (from LAM family) were responsible for outbreaks, respectively. In previous studies we demonstrated that these strains have differences on the development of host immune response. The complement system, besides its role in innate immunity, acts in the modulation of the adaptative response through the production of anaphylatoxins. Little is known about the role of complement system in immunity against Mtb infection. On this regard, it has been reported that C5a anaphylatoxin levels are elevated in tuberculosis patients compared to healthy donors and that this anaphylatoxin and it receptor are necessary for the granulomatous response to Mtb TDM. Besides, it has been reported that C5a anaphylatoxin suppress the production of IL-12 by IFNg-primed and LPS challenged human monocytes. C5a has two receptors: C5aR and C5L2. Recent studies have reported that C5aR activation in mouse dendritic cells (DC) regulates the differentiation of näive T cells towards Th1, Th17 and Treg. The function of C5L2 is controversial: while some studies postulate a scavenger role, others argue that it participates on the induction of a Th2 response profile. In this work we determined C5a receptors expression on ex vivo monocytes from healthy donors and TB patients, as well as in vitro PBMC derived monocytes stimulated with Ra, M and H37Rv strains. In addition, the role of monocytes´ C5aR on CD4+ T cells expression of IFNg, IL-4 and IL-21 was analyzed. Our preliminary results shows that C5L2 MFI was increased in TB, while not differences were found in C5aR. In vitro, both receptors were modulated in CD14+ cells and were not dependent on the strain. Finally, the blockage of C5aR in CD14+ cells enhanced the levels of CD4+IFNg+ cells induced by M strain. Therefore, these results suggest a role of C5aR in the modulation of IFNg by M strain.