Kinetics of cytokine gene expression in experimental chagasic cardiomyopathy: tissue parasitism and endogenous IFN-γ as important determinants of chemokine mRNA expression during infection with

Trypanosoma cruzi-elicited CD8+ T cell-mediated myocarditis: chemokine receptors and adhesion molecules as potential therapeutic targets to control chronic inflammation?

“…Further, using knockout mice infected with T. cruzi we showed that both IFN-γ and TNF-α are essential for the production of RANTES and MIP-1α, respectively (Aliberti et al 2001). Also, IFN-γ enhanced the in vitro production of RANTES and IP-10 by macrophages infected with T. cruzi or treated with glycosylphosphatidylinositol-anchored mucin-like glycoproteins of trypomastigotes (tGPI-mucins) (Talvani et al 2000, Aliberti et al 2001). Thus, it is possible that IFN-γ-induced chemokines present in the cardiac tissue o T. cruzi-infected individuals could also participate in parasitism control.…”

“…These cytokines are present in the inflamed heart of chronic chagasic patients (D'avila Reis et al 1993, and acute and chronic experimentally T. cruziinfected mice (Powell et al 1998, Talvani et al 2000, dos Santos et al 2001, suggesting that besides contributing to parasitism control they could be also involved in the maintenance of chronic myocarditis (Brener & Gazzinelli 1997, Abrahamsohn 1998). Recently we showed that the heart and central nervous system are the main sites of reactivation of T. cruzi infection in mice lacking functional genes for IFN-γ and IL-12, respectively (Michailowsky et al 2001).…”

“…Also, the inflamed tissue presents pro-inflammatory cytokines (IFN-γ, TNF-α) and chemokines (RANTES, MIP-1α, JE/MCP-1). These might selectively and preferentially recruit CD8 + T cells leading to the establishment of CD8-mediated myocarditis (Talvani et al 2000, dos Santos et al 2001. Novel therapeutic strategies aiming at limiting the inflammatory damage of cardiomyocytes, targeting integrin-mediated adhesion and chemokine-driven recruitment of leukocytes, besides the specific anti-T. cruzi drugs, should be evaluated.…”

CC-chemokine receptors: a potential therapeutic target for Trypanosoma cruzi-elicited myocarditis

“…Further, increased levels of CCL5/RANTES, CCL3/MIP-1α, CCL4/ MIP-1β, CCL2/MCP-1 and the CXC chemokines CXCL10/ IP-10 and CXCL9/MIG mRNA have been detected in the heart tissue of acutely and chronically T. cruzi-infected mice (Talvani et al 2000, Aliberti et al 2001, dos Santos et al 2001, Marino et al 2004, implicating a potential role for these molecules in Chagas disease.…”

“…Although slight, the decreased expression of CCL3/MIP-1α might be related with the decreased numbers of CD8 + cells into the heart tissue of Met-RANTES-treated infected mice, as these cells are the main producers of this chemokine (Cook et al 1999). On the other hand, the fact that T. cruzi-infected cardiomyocytes and macrophages produce large amounts of CCL5/RANTES and CCL2/MCP-1 (Machado et al 2000, Talvani et al 2000, could explain the finding showing that parasite growth was not hampered in Met-RANTEStreated mice as these CC-chemokines, particularly CCL2/ MCP-1, actively elicit parasite uptake and killing (Aliberti et al 1999). Altogether, our results point to the fact that this discreet change in chemokine pattern induced by Met-RANTES treatment was not sufficient to impair parasite control.…”