"The negative feedback mechanism between SLPI and IFNg is impaired in tuberculosis patients”.

TATEOSIAN, NANCY; PASQUINELLI, V; HERNANDEZ DEL PINO, R; GARCIA, V; CHULUYAN, E

Boston

Congreso; American Assosiation of Immunologists. 99th Annual Meeting of the American Association of Immunologists; 2012

American Assosiation of Immunologists

Mycobacterium tuberculosis increases IFNã secretion which plays an important role in granuloma formation and clearance of it. Also, the exposure of macrophages to M. tuberculosis increases secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor with antimycobacterial activity. Therefore, the aim of the present study was to determine the role of a putative interaction between IFNã and SLPI in PBMC derived from healthy donors (HD) and tuberculosis patients (TB). Peripheral blood mononuclear cells (PBMC) from TB and HD were treated with Mtb antigen and IFNã and SLPI was determined by ELISA. Our results showed that the stimulation with Mtb of PBMC from HD, it decreased SLPI (p<0.01) while increased IFNã secretion. Furthermore, the blockage of IFNã reversed the effect of the Mtb antigen on SLPI secretion in PBMC-derived HD. Surprisingly Mtb antigen did not modify the SLPI secretion in PBMC-derived from TB, although it increased IFNã. Furthermore, the mAb against IFNã did not affect the SLPI secretion. When plasma levels of SLPI and IFNã were measured, we found a positive correlation between them in TB but not in HD. Moreover, tuberculosis patients showed more SLPI in plasma, being the levels higher with the severity of the disease. Overall, these results suggest that there is a negative cross talk between IFNã and SLPI in HD that it is not present in TB patients. Therefore, the higher concentration of IFNã and SLPI might contribute to control the infection.