INVESTIGADORES
CARRERA SILVA Eugenio Antonio
artículos
Título:
Immunisation with a major Trypanosoma cruzi antigen promotes pro-inflammatory cytokines, nitric oxide production and increases TLR2 expression
Autor/es:
NATALIA GUIÑAZÚ; ANDREA PELLEGRINI; EUGENIO ANTONIO CARRERA SILVA; MARIA PILAR AOKI; ANA MARIA CABANILLAS; NURIA GÌRONÉS; MANUEL FRESNO; ROXANA CANO; SUSANA GEA
Revista:
INTERNATIONAL JOURNAL FOR PARASITOLOGY
Editorial:
ELSEVIER
Referencias:
Año: 2007 vol. 37 p. 1243 - 1254
ISSN:
0020-7519
Resumen:
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 immunisation of C57BL/6 mice with
cruzipain, an immunogenic T. cruzi glycoprotein, induced a strong
specific T-cell response. In this study, we demonstrated that active
immunisation with cruzipain was able to stimulate nitric oxide (NO)
production by splenocytes. Immune cells also showed increased inducible
nitric oxide synthase protein and mRNA expression. Spleen adherent
cells secreted high levels of IFN-g and IL-12. Microbicidal activity in
vitro was mainly mediated by reactive nitrogen intermediaries 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 TNF-a production. Furthermore, we reported that
cruzipain enhanced CD80 and major histocompatibility complex-II
molecule surface expression on F4/80+ spleen cells. Interestingly, we
also showed that cruzipain up-regulated toll like receptor-2 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, through adaptive immune
cells and cytokines, can modulate the macrophage response not only as
antigen presenting cells, but also as effector cells displaying
enhanced microbicidal activity with reactive nitrogen intermediary
participation. This may represent a mechanism that contributes to the
immunoregulatory process during Chagas disease.