title: The impact of IFN-γ receptor on SLPI expression in active tuberculosis: association with disease severity.
abstract: Interferon (IFN)-γ displays a critical role in tuberculosis (TB), 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). Herein, we determined whether IFN-γ modulated the levels of SLPI in TB patients. Plasma levels of SLPI and IFN-γ were studied in healthy donors (HDs) and TB patients. Peripheral blood mononuclear cells from HDs and patients with TB or defective IFN-γ receptor 1* were stimulated with Mtb antigen and SLPI, and IFN-γR expression levels were measured. Both SLPI and IFN-γ were significantly enhanced in plasma from those with TB compared with HDs. A direct association between SLPI levels and the severity of TB was detected. In addition, Mtb antigen stimulation decreased the SLPI produced by peripheral blood mononuclear cells from HDs, but not from TB or IFN-γR patients. Neutralization of IFN-γ reversed the inhibition of SLPI induced by Mtb antigen in HDs, but not in TB patients. Furthermore, recombinant IFN-γ was unable to modify the expression of SLPI in TB patients. Finally, IFN-γR expression was lower in TB compared with HD peripheral blood mononuclear cells. These results show that Mtb-induced IFN-γ down-modulated SLPI levels by signaling through the IFN-γR in HDs. This inhibitory mechanism was not observed in TB, probably because of the low expression of IFN-γR detected in these individuals.
authors.affiliation: Laboratory of Immunomodulators, School of Medicine, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET)-University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Tateosian
authors.affiliation: Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pasquinelli
authors.affiliation: Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Rodrigo E
authors.initials: RE
authors.lastname: Hernández Del Pino
authors.affiliation: Laboratory of Immunomodulators, School of Medicine, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET)-University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Nella
authors.initials: N
authors.lastname: Ambrosi
authors.affiliation: Laboratory of Immunomodulators, School of Medicine, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET)-University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Diego
authors.initials: D
authors.lastname: Guerrieri
authors.affiliation: Department of Biochemistry, National Institute of Medical Sciences Salvador Zubirán, Mexico City, Mexico.
authors.forename: Sigifredo
authors.initials: S
authors.lastname: Pedraza-Sánchez
authors.affiliation: Immunology Institute, School of Medicine, National University of Rosario, Rosario, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Santucci
authors.affiliation: Immunology Institute, School of Medicine, National University of Rosario, Rosario, Argentina.
authors.forename: Luciano
authors.initials: L
authors.lastname: D'Attilio
authors.affiliation: Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Pellegrini
authors.affiliation: Department of Clinic Genetics, Pediatric Hospital, Centro Médico Nacional siglo XXI. Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.
authors.forename: María A
authors.initials: MA
authors.lastname: Araujo-Solis
authors.affiliation: Tisioneumonology Division, Hospital F. J. Muñiz, Buenos Aires, Argentina.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Musella
authors.affiliation: Tisioneumonology Division, Hospital F. J. Muñiz, Buenos Aires, Argentina.
authors.forename: Domingo J
authors.initials: DJ
authors.lastname: Palmero
authors.affiliation: Department of Pathology, National Institute of Medical Sciences Salvador Zubirán, Mexico City, Mexico.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernandez-Pando
authors.affiliation: Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Verónica E
authors.initials: VE
authors.lastname: Garcia
authors.affiliation: Laboratory of Immunomodulators, School of Medicine, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET)-University of Buenos Aires, Buenos Aires, Argentina. Electronic address: echuluyan@fmed.uba.ar.
authors.forename: H Eduardo
authors.initials: HE
authors.lastname: Chuluyan
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism*; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000097:blood / Q000378:metabolism*; D012720:Severity of Illness Index; D014376:Tuberculosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology*
chemical_list: C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D007371:Interferon-gamma