Coinfection with different Trypanosoma cruzi strains interferes with the host immune response to infection.


Rodrigues, CM; Valadares, HM; Francisco, AF; Arantes, JM; Campos, CF; Teixeira-Carvalho, A; Martins-Filho, OA; Araujo, MS; Arantes, RM; Chiari, E; Franco, GR; Machado, CR; Pena, SD; Faria, AM; Macedo, AM; (2010) Coinfection with different Trypanosoma cruzi strains interferes with the host immune response to infection. PLoS neglected tropical diseases, 4 (10). e846. ISSN 1935-2727 DOI: https://doi.org/10.1371/journal.pntd.0000846

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Abstract

A century after the discovery of Trypanosoma cruzi in a child living in Lassance, Minas Gerais, Brazil in 1909, many uncertainties remain with respect to factors determining the pathogenesis of Chagas disease (CD). Herein, we simultaneously investigate the contribution of both host and parasite factors during acute phase of infection in BALB/c mice infected with the JG and/or CL Brener T. cruzi strains. JG single infected mice presented reduced parasitemia and heart parasitism, no mortality, levels of pro-inflammatory mediators (TNF-α, CCL2, IL-6 and IFN-γ) similar to those found among naïve animals and no clinical manifestations of disease. On the other hand, CL Brener single infected mice presented higher parasitemia and heart parasitism, as well as an increased systemic release of pro-inflammatory mediators and higher mortality probably due to a toxic shock-like systemic inflammatory response. Interestingly, coinfection with JG and CL Brener strains resulted in intermediate parasitemia, heart parasitism and mortality. This was accompanied by an increase in the systemic release of IL-10 with a parallel increase in the number of MAC-3(+) and CD4(+) T spleen cells expressing IL-10. Therefore, the endogenous production of IL-10 elicited by coinfection seems to be crucial to counterregulate the potentially lethal effects triggered by systemic release of pro-inflammatory mediators induced by CL Brener single infection. In conclusion, our results suggest that the composition of the infecting parasite population plays a role in the host response to T. cruzi in determining the severity of the disease in experimentally infected BALB/c mice. The combination of JG and CL Brener was able to trigger both protective inflammatory immunity and regulatory immune mechanisms that attenuate damage caused by inflammation and disease severity in BALB/c mice.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 20967289
Web of Science ID: 283559600016
URI: http://researchonline.lshtm.ac.uk/id/eprint/2131875

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