The role of fat on cardiomyopathy outcome in mouse models of chronic Trypanosoma cruzi infection

Paul Zaki, Elisa Lbc Domingues, Farhad M. Amjad, Maiara B. Narde, Karolina R. Gonçalves, Mirelle L. Viana, Heberth de Paula, Wanderson G. de Lima, Huan Huang, Maria T. Bahia, Philipp E. Sherer, Fabiane M. dos Santos, Louis M. Weiss, Herbert B. Tanowitz

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Abstract

The underlying pathogenic mechanisms of cardiomyopathy in Chagas disease are still unsolved. In order to better clarify the role of fat on the evolution of cardiomyopathy, the present study employed three murine models of chronic Trypanosoma cruzi infection: (1) aP2-RIDα/β transgenic mice (RID mice; an adipose tissue model which express a gain-of-function potent anti-inflammatory activity), (2) allograft inflammatory factor-1 knockout mice (Aif1−/−), and (3) a Swiss outbred mice. RID mice and non-transgenic mice (wild type, WT) were infected with blood trypomastigotes of Brazil strain. During the acute stage of infection, RID mice had lower parasitemia, lower heart inflammation, and a decrease in the relative distribution of parasite load from cardiac muscle tissue toward epididymal fat. Nevertheless, comparable profiles of myocardial inflammatory infiltrates and relative distribution of parasite load were observed among RID and WT at the chronic stage of infection. Aif1−/− and Aif1+/+ mice were infected with bloodstream trypomastigotes of Tulahuen strain and fed with high-fat diet (HFD) or regular diet (RD). Interestingly, Aif1+/+ HFD infected mice showed the highest mortality. Swiss mice infected with blood trypomastigotes of Berenice-78 strain on a HFD had higher levels of TNFα and more inflammation in their heart tissue than infected mice fed a RD. These various murine models implicate adipocytes in the pathogenesis of chronic Chagas disease and suggest that HFD can lead to a significant increase in the severity of parasite-induced chronic cardiac damage. Furthermore, these data implicate adipocyte TLR4-, TNFα-, and IL-1β-mediated signaling in pro-inflammatory pathways and Aif-1 gene expression in the development of chronic Chagas disease.

Original languageEnglish (US)
JournalParasitology research
DOIs
StateAccepted/In press - Jan 1 2020

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Keywords

  • Adipose tissue
  • Aif-1
  • Fat pro-inflammatory pathway
  • High-fat diet
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Parasitology
  • veterinary(all)
  • Insect Science
  • Infectious Diseases

Cite this

Zaki, P., Domingues, E. L., Amjad, F. M., Narde, M. B., Gonçalves, K. R., Viana, M. L., de Paula, H., de Lima, W. G., Huang, H., Bahia, M. T., Sherer, P. E., dos Santos, F. M., Weiss, L. M., & Tanowitz, H. B. (Accepted/In press). The role of fat on cardiomyopathy outcome in mouse models of chronic Trypanosoma cruzi infection. Parasitology research. https://doi.org/10.1007/s00436-020-06645-z