Abstract
CD43 (leukosialin) is a large sialoglycoprotein abundantly expressed on the surface of most cells from the hematopoietic lineage. CD43 is directly involved in the contact between cells participating in a series of events such as signaling, adherence and host parasite interactions. In this study we examined the role of CD43 in the immune response against Trypanosoma cruzi, the protozoan parasite that causes Chagas’ disease, a potential life-threatening illness endemic in 21 Latin American countries according to the WHO. The acute stage of infection is marked by intense parasitemia and cardiac tissue parasitism, resulting in the recruitment of inflammatory cells and acute damage to the heart tissue. We show here that CD43−/− mice were more resistant to infection due to increased cytotoxicity of antigen specific CD8+ T cells and reduced inflammatory infiltration in the cardiac tissue, both contributing to lower cardiomyocyte damage. In addition, we demonstrate that the induction of acute myocarditis involves the engagement of CD43 cytoplasmic tripeptide sequence KRR to ezrin-radixin-moiesin cytoskeletal proteins. Together, our results show the participation of CD43 in different events involved in the pathogenesis of T. cruzi infection, contributing to a better overall understanding of the mechanisms underlying the pathogenesis of acute chagasic cardiomyopathy.
Highlights
CD43 (Leukosialin) is a heavily glycosylated mammalian mucin-like protein expressed on the surface of most hematopoietic cells[1]
CD43NGG mice have T cells that express a mutated form of CD43 in a key tripeptide sequence changed from KRR to NGG which was previously shown to be important for CD43 interaction with ezrin-radixin-moesin family of proteins, mediating CD43 effects on T cell migration[11]
The initial parasite replication was not affected by the lack of CD43, lower amounts of parasite DNA were found in the cardiac tissue of CD43−/− and CD43NGG mice when compared to WT (Fig. 1E), indicating a reduced parasite burden in the heart tissue that may explain, at least in part, the increased survival rate of both CD43−/− and CD43NGG mice
Summary
CD43 (Leukosialin) is a heavily glycosylated mammalian mucin-like protein expressed on the surface of most hematopoietic cells[1]. The inactive form os TcTS (TcTSY342H) acts as a lectin, binding to sialic acid in CD43 expressed in CD4+ T cells inducing cell proliferation and cytokine production[30]. Both active and inactive isoforms of TcTS might present distinct immunomodulatory properties on T cells[31]. We used CD43 mutant mice to further exam the role of CD43 in leukocyte activation and recruitment as well as T cell function during acute cardiomyopathy induced by T. cruzi infection
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