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J Leukoc Biol. 2009 Nov;86(5):1239-46. doi: 10.1189/jlb.0309187. Epub 2009 Jul 29.

CCL2/MCP-1 controls parasite burden, cell infiltration, and mononuclear activation during acute Trypanosoma cruzi infection.

Author information

1
Departamento de Imunologia, Instituto de Microbiologia Prof Paulo de Góes, UFRJ, Av. Carlos Chagas Filho 373, CCS Bloco I, Ilha do Fundão, Rio de Janeiro, RJ, Brazil 21941-902. cnpaiva@iname.com

Abstract

CCL2/MCP-1 has emerged recently as a critical factor in infectious and autoimmune myocarditis. In fact, this chemokine is produced in great amounts in hearts from Trypanosoma cruzi-infected mice and is known to enhance parasite uptake and destruction by macrophages. Herein, we studied the involvement of CCL2 in tissue inflammation and resistance to T. cruzi. Infected CCL2(-/-) mice developed higher parasitemias and died earlier than WT mice. Close to their death, T. cruzi-infected CCL2(-/-) presented greater amounts of TNF, IFN-gamma, and IL-10 in plasma than WTs and clinical signs of systemic inflammatory response. Amastigote nests were more frequent in hearts and livers from infected CCL2(-/-) tissues than in WTs, and reduced numbers of leukocytes infiltrated their tissues. Leukocytes formed diffuse but not focal infiltrates in hearts from infected CCL2(-/-) mice, and perivascular cuffs could still be found in their livers. Infected CCL2(-/-) mice had smaller percentages of activated CD11b (Mac-1)+CD107b (Mac-3)+ macrophages and CD8+CD69(hi) cells among heart and liver infiltrates than WTs (flow cytometry), indicating that CCL2 controls subset migration/activation. CCL2 accumulated among focal heart infiltrates, suggesting that this chemokine is involved in retention of mononuclear cells in particular spots. Peritoneal macrophages from CCL2(-/-) mice displayed decreased trypanocidal activity. Our results demonstrate that CCL2 contributes to reduce parasite growth and indicate that it does so by controlling the distribution, cellular composition, and state of activation of inflammatory infiltrates in acute T. cruzi infection.

PMID:
19641038
DOI:
10.1189/jlb.0309187
[Indexed for MEDLINE]

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