Cross-talk between CD31 and the signaling lymphocytic activation molecule-associated protein during interferon- gamma production against Mycobacterium tuberculosis

QUIROGA MARÍA; JURADO JAVIER; MARTÍNEZ GUSTAVO; PASQUINELLI VIRGINIA; MUSELLA ROSA; ABBATE EDUARDO; ISSEKUTZ ANDREW; SIELING PETER; CHULUYAN EDUARDO; GARCÍA VERÓNICA

JOURNAL OF INFECTIOUS DISEASES

Infectious Diseases Society of America

Lugar: Arlington, VA ; Año: 2007 vol. 196 p. 1369 - 1378

0022-1899

Effective host defense against tuberculosis requires Th1 cytokine responses. We studied the regulation of interferon (IFN)-g 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-g 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-g production was low. Furthermore, the inverse relationship between CD31 expression and IFN-g production was in contrast to signaling lymphocytic activation molecule (SLAM) expression, an IFN-g inducer in tuberculosis. Interestingly, CD31 bound to SLAM-associated protein (SAP), an IFN-g inhibitor in tuberculosis, and when CD31 and SAP were coexpressed in lymphocytes, their association inhibited the IFN-g 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 IFNg response to M. tuberculosis.g 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-g 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-g production was low. Furthermore, the inverse relationship between CD31 expression and IFN-g production was in contrast to signaling lymphocytic activation molecule (SLAM) expression, an IFN-g inducer in tuberculosis. Interestingly, CD31 bound to SLAM-associated protein (SAP), an IFN-g inhibitor in tuberculosis, and when CD31 and SAP were coexpressed in lymphocytes, their association inhibited the IFN-g 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 IFNg response to M. tuberculosis.