The impact of IFN-g receptor on SLPI expression in active tuberculosis: association with disease severity

TATEOSIAN NL; PASQUINELLI V; HERNÁNDEZ DEL PINO RE; AMBROSI N; GUERRIERI D; PEDRAZA SANCHEZ, S; SANTUCCI N; D´ATTILIO L; PELLEGRINI J; ARAUJO-SOLIS MARÍA A; MUSELLA RM; PALMERO DJ; HERNANDEZ- PANDO R; GARCÍA VE; CHULUYAN HE

AMERICAN JOURNAL OF PATHOLOGY

AMER SOC INVESTIGATIVE PATHOLOGY, INC

Lugar: Bethesda ; Año: 2014 vol. 184 p. 1268 - 1273

0002-9440

IFN-g displays a critical role in tuberculosis disease, modulating the innate and adaptive immune responses. Previously we reported that secretory leukocyte protease inhibitor (SLPI) is a pattern recognition receptor with anti-mycobacterial activity against Mycobacterium tuberculosis (Mtb). The aim of the present work was to determine whether IFN-g modulated the levels of SLPI in tuberculosis patients. Plasma levels of SLPI and IFN-g were studied in healthy donors (HD) and tuberculosis (TB) patients. PBMC from HD and patients with TB or defective IFN-g receptor (IFNGR1*) were stimulated with Mtb-antigen and SLPI and IFN-gR expression were measured. Both SLPI and IFN-g were significantly enhanced in plasma from TB as compare to HD. A direct association between SLPI levels and the severity of TB disease was detected. Besides, Mtb-antigen stimulation decreased the SLPI produced by PBMC from HD but not from TB or IFNGR1* patients. Neutralization of IFN-g reversed the inhibition of SLPI induced by Mtb-antigen in HD but not in TB patients. Furthermore, rIFN-g was unable to modify the expression of SLPI in TB patients. Finally, IFN-g expression was lower in TB as compared to HD PBMCs. These results show that Mtb-induced IFN-g down-modulated SLPI levels by signaling through the IFN-gR in HD. This inhibitory mechanism was not observed in TB, probably due to the low expression of IFN-g receptor detected in these individuals.