title: Cross-talk between CD31 and the signaling lymphocytic activation molecule-associated protein during interferon- gamma production against Mycobacterium tuberculosis.
abstract: Effective host defense against tuberculosis requires Th1 cytokine responses. We studied the regulation of interferon (IFN)- gamma production during tuberculosis by investigating the role of CD31, a receptor that attenuates T cell receptor signals. After antigen stimulation, CD3(+)CD31(+) blood lymphocytes decreased in healthy donors and in tuberculosis patients with robust Th1 responses to Mycobacterium tuberculosis and IFN- gamma was secreted only by CD31(-) T cells. In contrast, in patients with weak Th1 cytokine responses to M. tuberculosis, the level of CD3(+)CD31(+) lymphocytes was increased and IFN- gamma production was low. Furthermore, the inverse relationship between CD31 expression and IFN- gamma production was in contrast to signaling lymphocytic activation molecule (SLAM) expression, an IFN- gamma inducer in tuberculosis. Interestingly, CD31 bound to SLAM-associated protein (SAP), an IFN- gamma inhibitor in tuberculosis, and when CD31 and SAP were coexpressed in lymphocytes, their association inhibited the IFN- gamma response to M. tuberculosis. Thus, CD31, when binding to SAP, interferes with Th1 responses, suggesting that CD31 has a key regulatory role in the signaling pathway(s) leading to the IFN- gamma response to M. tuberculosis.
authors.affiliation: Department of Microbiology, Parasitology, and Immunology, University of Buenos Aires School of Medicin, Buenos Aires, Argentina.
authors.forename: Maria Florencia
authors.initials: MF
authors.lastname: Quiroga
authors.forename: Javier Oscar
authors.initials: JO
authors.lastname: Jurado
authors.forename: Gustavo Javier
authors.initials: GJ
authors.lastname: Martínez
authors.forename: Virginia
authors.initials: V
authors.lastname: Pasquinelli
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Musella
authors.forename: Eduardo
authors.initials: E
authors.lastname: Abbate
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Issekutz
authors.forename: María Marta
authors.initials: MM
authors.lastname: Bracco
authors.forename: Alejandro
authors.initials: A
authors.lastname: Malbran
authors.forename: Peter Allan
authors.initials: PA
authors.lastname: Sieling
authors.forename: Eduardo
authors.initials: E
authors.lastname: Chuluyan
authors.forename: Verónica Edith
authors.initials: VE
authors.lastname: García
mesh_terms: D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D015398:Signal Transduction; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D013601:T-Lymphocytes / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D007371:Interferon-gamma