MyD88 activation in cardiomyocytes contributes to the heart immune response to acute Trypanosoma cruzi infection with no effect on local parasite control

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Santana, Danni Yohani ^{[1, 2]} ; Salgado, Rafael Moyses ^{[1, 2]} ; Fevereiro, Marina ^{[1, 3]} ; do Nascimento, Rogerio Silva ^{[1, 2]} ; Fonseca, Raissa ^{[1, 2]} ; Saraiva Camara, Niels Olsen ^{[1, 2]} ; Epiphanio, Sabrina ^[4] ; Farias Marinho, Claudio Romero ^{[1, 5]} ; Barreto-Chaves, Maria Luiza ^{[1, 3]} ; D' Imperio-Lima, Maria Regina ^{[1, 2]} ; Alvarez, Jose M. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Dept Immunol, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Dept Anat, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Dept Clin & Toxicol Anal, Fac Pharm, Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Dept Parasitol, Fac Pharm, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 12, n. 8 AUG 2018.
• Citações Web of Science: 0

Resumo

Cardiomyopathy is the most serious consequence of Chagas disease, a neglected human disorder caused by Trypanosoma cruzi infection. Because T. cruzi parasites invade cardiomyocytes, we sought to investigate whether these cells recognize the parasite in vivo by receptors signaling through the MyD88 adaptor, which mediates the activation pathway of most Toll-like receptors (TLRs) and IL-1/IL-18 receptors, and influence the development of acute cardiac pathology. First, we showed that HL-1 cardiac muscle cell line expresses MyD88 gene and protein at resting state and after T. cruzi infection. To evaluate the role in vivo of MyD88 expression in cardiomyocytes, we generated Mer (+)MyD88flox(+/+) mice in which tamoxifen treatment is expected to eliminate the MyD88 gene exclusively in cardiomyocytes. This Cre-loxP model was validated by both PCR and western blot analysis; tamoxifen treatment of Mer(+)MyD88flox(+/+) mice resulted in decreased MyD88 gene and protein expression in the heart, but not in the spleen, while had no effect on littermates. The elimination of MyD88 in cardiomyocytes determined a lower increase in CCL5, IFN gamma and TNF alpha gene transcription during acute infection by T. cruzi parasites of the Y strain, but it did not significantly modify heart leukocyte infiltration and parasitism. Together, our results show that cardiomyocytes can sense T. cruzi infection through MyD88-mediated molecular pathways and contribute to the local immune response to the parasite. The strong pro-inflammatory response of heart-recruited leukocytes may overshadow the effects of MyD88 deficiency in cardiomyocytes on the local leukocyte recruitment and T. cruzi control during acute infection. (AU)

• Processo FAPESP: 13/08199-0 - Estudo da infecção murina pelo clone de Trypanosoma cruzi Sylvio X10/4, um parasita de baixa virulência
• Beneficiário: José Maria Álvarez Mosig
• Modalidade de apoio: Auxílio à Pesquisa - Regular