The negative feedback mechanism between SLPI and IFNγ is impaired in tuberculosis patients (164.7)

Abstract

Abstract Mycobacterium tuberculosis increases IFNγ 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 IFNγ 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 IFNγ 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 IFNγ secretion. Furthermore, the blockage of IFNγ 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 IFNγ. Furthermore, the mAb against IFNγ did not affect the SLPI secretion. When plasma levels of SLPI and IFNγ 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 IFNγ and SLPI in HD that it is not present in TB patients. Therefore, the higher concentration of IFNγ and SLPI might contribute to control the infection.