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Trypanosoma cruzi infection induces the expression of CD40 in murine cardiomyocytes favoring CD40 ligation-dependent production of cardiopathogenic IL-6

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Abstract

The inflammatory response in the myocardium is an important aspect of the pathogenesis of Chagas’ heart disease raised by Trypanosoma cruzi. CD40, a transmembrane type I receptor belonging to the tumor necrosis factor receptor (TNFR) family, is expressed in a broad spectrum of cell types and is crucial in several inflammatory and autoimmune diseases. Activation of CD40 through ligation to CD40L (CD154) induces multiple effects, including the secretion of proinflammatory molecules. In the present study, we examined the ability of T. cruzi to trigger the expression of CD40 in cardiac myocytes in vitro and in a murine model of chagasic cardiomyopathy. Our results indicate, for the first time, that T. cruzi is able to induce the expression of CD40 in HL-1 murine cardiomyocytes. Moreover, ligation of CD40 receptor upregulated interleukin-6 (IL-6), associated with inflammation. Furthermore, the induction of this costimulatory molecule was demonstrated in vivo in myocardium of mice infected with T. cruzi. This suggests that CD40-bearing cardiac muscle cells could interact with CD40L-expressing lymphocytes infiltrating the heart, thus contributing to inflammatory injury in chagasic cardiomyopathy.

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Acknowledgments

This work was supported in part by grants from the National Research Council (CONICET, Argentina). P.B.P., R.S.C., and M.P. are members of the Research Career Program from CONICET. A.C. thanks UBA for the fellowship granted. M.A.M.A. and M.N.G. thank CONICET for the fellowship granted. HL-1 cells were a gift from Dr. W. C. Claycomb (Louisiana State University, New Orleans, LA, USA).

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    Authors and Affiliations

    1. Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, Buenos Aires, Argentina

      Mariela Alejandra Moreno Ayala, Agustina Casasco, Ricardo Santiago Corral & Patricia Beatriz Petray

    2. Instituto de Investigaciones Biomédicas (UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 10, Buenos Aires, Argentina

      Mariela Alejandra Moreno Ayala

    3. Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 13, Buenos Aires, Argentina

      Agustina Casasco & Patricia Beatriz Petray

    4. Instituto Nacional de Parasitología Dr. Mario Fatala Chabén/ANLIS/Malbrán, Av. Paseo Colón 568, Buenos Aires, Argentina

      Mariela González & Miriam Postan

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    1. Mariela Alejandra Moreno Ayala
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    2. Agustina Casasco
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    3. Mariela González
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    4. Miriam Postan
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    5. Ricardo Santiago Corral
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    6. Patricia Beatriz Petray
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    Correspondence to Patricia Beatriz Petray.

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    Mariela Alejandra Moreno Ayala and Agustina Casasco contributed equally to this work.

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    Moreno Ayala, M.A., Casasco, A., González, M. et al. Trypanosoma cruzi infection induces the expression of CD40 in murine cardiomyocytes favoring CD40 ligation-dependent production of cardiopathogenic IL-6. Parasitol Res 115, 779–785 (2016). https://doi.org/10.1007/s00436-015-4805-4

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    • DOI: https://doi.org/10.1007/s00436-015-4805-4

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