Previous Article | Next Article ![]()
Infection and Immunity, September 1999, p. 4819-4826, Vol. 67, No. 9
Department of Immunology,
Received 2 March 1999/Returned for modification 16 April
1999/Accepted 27 May 1999
In the present study, we describe the ability of Trypanosoma
cruzi trypomastigotes to stimulate the synthesis of
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
-Chemokines Enhance Parasite Uptake and Promote
Nitric Oxide-Dependent Microbiostatic Activity in Murine Inflammatory
Macrophages Infected with Trypanosoma cruzi
-chemokines by macrophages. In vivo infection with T. cruzi led to MIP-1
, RANTES, and JE/MCP1 mRNA expression by
cells from peritoneal inflammatory exudate. In addition, in vitro
infection with T. cruzi resulted in expression of
-chemokine MIP-1
, MIP-1
, RANTES, and JE mRNA by macrophages.
The expression of the
-chemokine MIP-1
, MIP-1
, RANTES, and JE
proteins by murine macrophages cultured with trypomastigote forms of
T. cruzi was confirmed by immunocytochemistry.
Interestingly, macrophage infection with T. cruzi also
resulted in NO production, which we found to be mediated mainly by
-chemokines. Hence, treatment with anti-
-chemokine-specific
neutralizing antibodies partially inhibited NO release by macrophages
incubated with T. cruzi parasites. Further, the addition of
the exogenous
-chemokines MIP-1
, MIP-1
, RANTES, and JE/MCP-1
induced an increased T. cruzi uptake, leading to enhanced
NO production and control of parasite replication in a dose-dependent
manner. L-NMMA, a specific inhibitor of the L-arginine-NO pathway, caused a decrease in NO production
and parasite killing when added to cultures of macrophages stimulated with
-chemokines. Among the
-chemokines tested, JE was more potent in inhibiting parasite growth, although it was much less efficient than gamma interferon (IFN-
). Nevertheless, JE potentiates parasite killing by macrophages incubated with low doses of IFN-
. Together, these results suggest that in addition to their chemotactic activity, murine
-chemokines may also contribute to enhancing parasite uptake and promoting control of parasite replication in
macrophages and may play a role in resistance to T. cruzi infection.
*
Corresponding author. Mailing address: Department of
Immunology, FMRP/USP, Ribeirão Preto-SP, 14049-900, Brazil.
Phone: 55-16-602-3234. Fax: 55-16-633-6631. E-mail:
jsdsilva{at}fmrp.usp.br.
Infection and Immunity, September 1999, p. 4819-4826, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|