Role of SOCS2 in modulating heart damage and function in a murine model of acute Chagas disease

Lisia Esper, Danilo Roman-Campos, Aline Lara, Fatima Brant, Luisa L. Castro, Andreia Barroso, Ronan Ricardo S Araujo, Leda Q. Vieira, Shankar Mukherjee, Eneas Ricardo M Gomes, Nazareth N. Rocha, Isalira P R Ramos, Michael P. Lisanti, Camila F. Campos, Rosa M E Arantes, Silvia Guatimosim, Louis M. Weiss, Jader Santos Cruz, Herbert B. Tanowitz, Mauro M. TeixeiraFabiana S. Machado

Research output: Contribution to journalArticle

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Abstract

Infection with Trypanosoma cruzi induces inflammation, which limits parasite proliferation but may result in chagasic heart disease. Suppressor of cytokine signaling 2 (SOCS2) is a regulator of immune responses and may therefore participate in the pathogenesis of T. cruzi infection. SOCS2 is expressed during T. cruzi infection, and its expression is partially reduced in infected 5-lipoxygenase-deficient [knockout (KO)] mice. In SOCS2 KO mice, there was a reduction in both parasitemia and the expression of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-6, IL-10, SOCS1, and SOCS3 in the spleen. Expression of IFN-γ, TNF-α, SOCS1, and SOCS3 was also reduced in the hearts of infected SOCS2 KO mice. There was an increase in the generation and expansion of T regulatory (Treg) cells and a decrease in the number of memory cells in T. cruzi-infected SOCS2 KO mice. Levels of lipoxinA 4 (LXA 4) increased in these mice. Echocardiography studies demonstrated an impairment of cardiac function in T. cruzi-infected SOCS2 KO mice. There were also changes in calcium handling and in action potential waveforms, and reduced outward potassium currents in isolated cardiac myocytes. Our data suggest that reductions of inflammation and parasitemia in infected SOCS2-deficient mice may be secondary to the increases in Treg cells and LXA 4 levels. This occurs at the cost of greater infection-associated heart dysfunction, highlighting the relevance of balanced inflammatory and immune responses in preventing severe T. cruzi-induced disease.

Original languageEnglish (US)
Pages (from-to)130-140
Number of pages11
JournalAmerican Journal of Pathology
Volume181
Issue number1
DOIs
StatePublished - Jul 2012

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Chagas Disease
Acute Disease
Trypanosoma cruzi
Knockout Mice
Cytokines
Parasitemia
Regulatory T-Lymphocytes
Infection
Interferons
Tumor Necrosis Factor-alpha
Inflammation
Arachidonate 5-Lipoxygenase
Cardiac Myocytes
Interleukin-10
Action Potentials
Echocardiography
Heart Diseases
Interleukin-6
Potassium
Parasites

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Esper, L., Roman-Campos, D., Lara, A., Brant, F., Castro, L. L., Barroso, A., ... Machado, F. S. (2012). Role of SOCS2 in modulating heart damage and function in a murine model of acute Chagas disease. American Journal of Pathology, 181(1), 130-140. https://doi.org/10.1016/j.ajpath.2012.03.042

Role of SOCS2 in modulating heart damage and function in a murine model of acute Chagas disease. / Esper, Lisia; Roman-Campos, Danilo; Lara, Aline; Brant, Fatima; Castro, Luisa L.; Barroso, Andreia; Araujo, Ronan Ricardo S; Vieira, Leda Q.; Mukherjee, Shankar; Gomes, Eneas Ricardo M; Rocha, Nazareth N.; Ramos, Isalira P R; Lisanti, Michael P.; Campos, Camila F.; Arantes, Rosa M E; Guatimosim, Silvia; Weiss, Louis M.; Cruz, Jader Santos; Tanowitz, Herbert B.; Teixeira, Mauro M.; Machado, Fabiana S.

In: American Journal of Pathology, Vol. 181, No. 1, 07.2012, p. 130-140.

Research output: Contribution to journalArticle

Esper, L, Roman-Campos, D, Lara, A, Brant, F, Castro, LL, Barroso, A, Araujo, RRS, Vieira, LQ, Mukherjee, S, Gomes, ERM, Rocha, NN, Ramos, IPR, Lisanti, MP, Campos, CF, Arantes, RME, Guatimosim, S, Weiss, LM, Cruz, JS, Tanowitz, HB, Teixeira, MM & Machado, FS 2012, 'Role of SOCS2 in modulating heart damage and function in a murine model of acute Chagas disease', American Journal of Pathology, vol. 181, no. 1, pp. 130-140. https://doi.org/10.1016/j.ajpath.2012.03.042
Esper, Lisia ; Roman-Campos, Danilo ; Lara, Aline ; Brant, Fatima ; Castro, Luisa L. ; Barroso, Andreia ; Araujo, Ronan Ricardo S ; Vieira, Leda Q. ; Mukherjee, Shankar ; Gomes, Eneas Ricardo M ; Rocha, Nazareth N. ; Ramos, Isalira P R ; Lisanti, Michael P. ; Campos, Camila F. ; Arantes, Rosa M E ; Guatimosim, Silvia ; Weiss, Louis M. ; Cruz, Jader Santos ; Tanowitz, Herbert B. ; Teixeira, Mauro M. ; Machado, Fabiana S. / Role of SOCS2 in modulating heart damage and function in a murine model of acute Chagas disease. In: American Journal of Pathology. 2012 ; Vol. 181, No. 1. pp. 130-140.
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AU - Barroso, Andreia

AU - Araujo, Ronan Ricardo S

AU - Vieira, Leda Q.

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AU - Arantes, Rosa M E

AU - Guatimosim, Silvia

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AU - Cruz, Jader Santos

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