Cruzipain, a major Trypanosoma cruzi antigen, promotes pro-inflammatory cytokines, nitric oxide production and increases TLR2 expression

NATALIA GUIÑAZÚ, ANDREA PELLEGRINI, EUGENIO ANTONIO CARRERA-SILVA, MARIA PILAR AOKI, ANA MARIA CABANILLAS, NURIA GÌRONÉS, MANUEL FRESNO, ROXANA CANO, SUSANA GEA

INFECTION AND IMMUNITY

American Society for Microbiology

Lugar: Washington; Año: 2006

0019-9567

Innate and adaptive immunity collaborate in the protection of intracellular pathogens including Trypanosoma cruzi infection. However, the parasite molecules that regulate the host immune response have not been fully identified. We previously demonstrated that the immunization of C57BL/6 mice with cruzipain, an immunogenic T. cruzi antigen, induced a strong specific T-cell response. In this study, we demonstrated that active immunization with cruzipain was able to stimulate nitric oxide (NO) production by splenocytes. Immune cells also showed increased inducible nitric oxide synthase (iNOS) protein and mRNA expression. Spleen adherent cells, mainly composed of F4/80+, CD3+ and CD19+ cells, secreted high levels of gamma interferon (IFN-g) and interleukin-12 (IL-12). Microbicidal activity in vitro in macrophages was mainly mediated by NO and IFN-g, as demonstrated by the inhibitory effects of NO synthase inhibitor or by IFN-g neutralization. Specific T-cells were essential for NO, IFN-g and tumor necrosis factor alpha (TNF-a) production. Furthermore, we reported that cruzipain enhanced CD80 and major histocompatibility complex-II (MHC-II) molecules surface expression on F4/80+ spleen cells. We also demonstrated that cruzipain up-regulated toll like receptor- 2 (TLR2) expression, not only in F4/80+ but also in total spleen cells, which may be involved in the effector immune response. Our findings suggest that a single parasite antigen such as cruzipain in spleen macrophages modulates the production of NO and pro-inflammatory cytokines to enhance the microbicidal activity. This may represent a mechanism that participates in the immunoregulatory process during Chagas disease.