|
|
| Id: | 18227
| | Author: | Quiroga, Maria F; Martinez, Gustavo J; Pasquinelli, Virginia; Costas, Monica A; Bracco, Maria M; Malbran, Aleajndro; Olivares, Liliana M; Sieling, Peter A; Garcia, Veronica E
| | Title: | Activation of signaling lymphocytic activation molecule triggers a signaling cascade that enhances Th1 responses in human intracellular infection
..-
| | Source: | s.l; s.n; 2004. 10 p. graf.
| | Abstract: | T cell production of IFN-gamma contributes to host defense against infections by intracellular pathogens, including mycobacteria. Lepromatous leprosy, the dissminated from 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-gamma production. We have previously shown that ligation of signaling lymphocytic activation molecule (SLAM) enhances IFN-gamma in mycobacterial infection; therefore, we investigated molecular pathways leading from SLAM activation to IFN-gamma production in human leprosy. The expression of the SLAM-associated protein (an inhibitory factor for IFN-gamma induction) on M. leprae-stimulated cells from leprosy patients was inversely correlated to IFN-gamma production. Howevwe, SLAM ligation or exposure of cell from lepromatous patients to a proinflammatory microenvironment down-regulated SLAM-associated protein expression. Moreover. SALAM activation induced a sequence of signaling proteins, including activation of the NF-kB complex, phosphorylation of Stat1, and induction of T-bet expression, resulting in the promotion a cascade of molecular events during signaling through SLAM in leprosy that cooperate to induce INF-gamma production and strongly suggest that SLAM might be a focal point for therapeutic modulation of the cell cytokine responses in diseases characterized by dysfunctional Th2 responses (AU).
| | Descriptors: | HANSENIASE/imunol
HANSENIASE/microbiol
LINFOCITOS T/imunol
LINFOCITOS T/microbiol
INTERLEUCINAS/sangue
INTERLEUCINAS/imunol
- LINFOCITOS/imunol
LINFOCITOS/microbiol
MYCOBACTERIUM LEPRAE/imunol
MYCOBACTERIUM LEPRAE/patogen
| | Limits: | HUMANO
| | Location: | BR191.1; 09192/s |
|
