{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:56:33Z","timestamp":1788299793157,"version":"build-2803163510"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2004,9,1]],"date-time":"2004-09-01T00:00:00Z","timestamp":1093996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>T cell production of IFN-\u03b3 contributes to host defense against infection by intracellular pathogens, including mycobacteria. Lepromatous leprosy, the disseminated form of infection caused by Mycobacterium leprae, is characterized by loss of cellular response against the pathogen and diminished Th1 cytokine production. Relieving bacterial burden in Ag-unresponsive patients might be achieved through alternative receptors that stimulate IFN-\u03b3 production. We have previously shown that ligation of signaling lymphocytic activation molecule (SLAM) enhances IFN-\u03b3 in mycobacterial infection; therefore, we investigated molecular pathways leading from SLAM activation to IFN-\u03b3 production in human leprosy. The expression of the SLAM-associated protein (an inhibitory factor for IFN-\u03b3 induction) on M. leprae-stimulated cells from leprosy patients was inversely correlated to IFN-\u03b3 production. However, SLAM ligation or exposure of cells from lepromatous patients to a proinflammatory microenvironment down-regulated SLAM-associated protein expression. Moreover, SLAM activation induced a sequence of signaling proteins, including activation of the NF-\u03baB complex, phosphorylation of Stat1, and induction of T-bet expression, resulting in the promotion of IFN-\u03b3 production, a pathway that remains quiescent in response to Ag in lepromatous patients. Therefore, our findings reveal a cascade of molecular events during signaling through SLAM in leprosy that cooperate to induce IFN-\u03b3 production and strongly suggest that SLAM might be a focal point for therapeutic modulation of T cell cytokine responses in diseases characterized by dysfunctional Th2 responses.<\/jats:p>","DOI":"10.4049\/jimmunol.173.6.4120","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T02:57:29Z","timestamp":1398049049000},"page":"4120-4129","source":"Crossref","is-referenced-by-count":16,"title":["Activation of Signaling Lymphocytic Activation Molecule Triggers a Signaling Cascade That Enhances Th1 Responses in Human Intracellular Infection"],"prefix":"10.1093","volume":"173","author":[{"given":"Mari\u0301a F","family":"Quiroga","sequence":"first","affiliation":[{"name":"Department of Microbiology, Parasitology, and Immunology, University of Buenos Aires School of Medicine , Buenos Aires ,","place":["Argentina"]},{"name":"Laboratorio de Inmunogene\u0301tica, Hospital de Cli\u0301nicas Jose\u0301 de San Marti\u0301n, University of Buenos Aires , Buenos Aires ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo J","family":"Marti\u0301nez","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Parasitology, and Immunology, University of Buenos Aires School of Medicine , Buenos Aires ,","place":["Argentina"]},{"name":"Laboratorio de Inmunogene\u0301tica, Hospital de Cli\u0301nicas Jose\u0301 de San Marti\u0301n, University of Buenos Aires , Buenos Aires ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Pasquinelli","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Parasitology, and Immunology, University of Buenos Aires School of Medicine , Buenos Aires ,","place":["Argentina"]},{"name":"Laboratorio de Inmunogene\u0301tica, Hospital de Cli\u0301nicas Jose\u0301 de San Marti\u0301n, University of Buenos Aires , Buenos Aires ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo\u0301nica A","family":"Costas","sequence":"additional","affiliation":[{"name":"Laboratorio de Biologi\u0301a Molecular y Apoptosis, Instituto de Investigaciones Me\u0301dicas A. Lanari, University of Buenos Aires , Buenos Aires ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u0301a M","family":"Bracco","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Hematolo\u0301gicas, Academia Nacional de Medicina , Buenos Aires ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Malbra\u0301n","sequence":"additional","affiliation":[{"name":"Departamento de Alergia e Inmunologi\u0301a, Hospital Brita\u0301nico , Buenos Aires ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana M","family":"Olivares","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Leprosy Section, Hospital de Infecciosas F. J. Mun\u0303iz , Buenos Aires ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A","family":"Sieling","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California , Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vero\u0301nica E","family":"Garci\u0301a","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Parasitology, and Immunology, University of Buenos Aires School of Medicine , Buenos Aires ,","place":["Argentina"]},{"name":"Laboratorio de Inmunogene\u0301tica, Hospital de Cli\u0301nicas Jose\u0301 de San Marti\u0301n, University of Buenos Aires , Buenos Aires ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,9,15]]},"reference":[{"key":"2025032617340685600_R1","first-page":"44","volume-title":"Chem. 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