Role of C5a anaphylotoxin receptors in the immune response

SABIO Y GARCÍA, CARMEN; ; GEFFNER, LAURA; ; YOKOBORI, NOEMI; ; GONZALEZ, ALEJANDRA; ; ASQUINEYER, YANINA; ; LÓPEZ, BEATRIZ; ; DE LA BARRERA, SILVIA; ; SASIAIN, M. DEL CARMEN.

Congreso; Primer Congreso Franco-Argentino de Inmunología; 2010

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is capable of establishing a niche inside the macrophage, where it can survive and replicate. Once the infection has occurred, a successful immune response requires the activation of a Th1 response. The complement system, besides its role in innate immunity, acts in the modulation of the adaptative response through the production of proinflammatory anaphylatoxins. Recent studies report that C5a receptor (C5aR) activation in dendritic cells (DC) induces innate immune signals which regulates the differentiation of näive cells into Th1, Th17 and Treg. In this context, we aim to investigate the effect of C5aR and C5L2 in the modulation of the Th1/Th17 profile in the immune response against local strains of Mtb. The expression of both receptors was evaluated ex vivo and in cultured monocytes from healthy donors (N) and patients with active TB. Monocytes were stimulated with 2 local MDR clinical isolates (M or Ra) or H37Rv for 48 hr. The expression of C5aR and C5L2 in CD14+ cells was measured by flow cytometry. To evaluate whether C5aR modulates IFNγ and IL-21 expression in CD4+ T cells, monocytes were cultured with Mtb in the presence of anti-C5aR for 18hs; then, autologue T cells were added and IFNγ and IL-21 expression in CD4+ subset was determined by flow cytometry. Although no differences were found in C5aR expression in CD14+ between patients and N ex vivo, C5L2 was increased in TB patients (p<0.05). All Mtb strains diminished C5aR expression in CD14+ while C5L2 was increased (p<0.05). Preliminary blockade results suggest that IFNγ and IL-21 expression was differentially modified by C5aR in CD4+. These results suggest that C5a receptors could be modulating T cell responses against Mtb.