MyD88 activation in cardiomyocytes contributes to the heart immune response to acute Trypanosoma cruzi infection with no effect on local parasite control.
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 a...
Published in: | PLOS Neglected Tropical Diseases |
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2018
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ftdoajarticles:oai:doaj.org/article:6b89d81dc8f84510916bbbb27095f04b 2023-05-15T15:13:39+02:00 MyD88 activation in cardiomyocytes contributes to the heart immune response to acute Trypanosoma cruzi infection with no effect on local parasite control. Danni Yohani Santana Rafael Moysés Salgado Marina Fevereiro Rogério Silva do Nascimento Raissa Fonseca Niels Olsen Saraiva Câmara Sabrina Epiphanio Cláudio Romero Farias Marinho Maria Luiza Barreto-Chaves Maria Regina D' Império-Lima José M Álvarez 2018-08-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006617 https://doaj.org/article/6b89d81dc8f84510916bbbb27095f04b EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC6089445?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006617 https://doaj.org/article/6b89d81dc8f84510916bbbb27095f04b PLoS Neglected Tropical Diseases, Vol 12, Iss 8, p e0006617 (2018) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2018 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006617 2022-12-31T03:40:26Z 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, IFNγ and TNFα 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic The ''Y'' ENVELOPE(-112.453,-112.453,57.591,57.591) PLOS Neglected Tropical Diseases 12 8 e0006617 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Danni Yohani Santana Rafael Moysés Salgado Marina Fevereiro Rogério Silva do Nascimento Raissa Fonseca Niels Olsen Saraiva Câmara Sabrina Epiphanio Cláudio Romero Farias Marinho Maria Luiza Barreto-Chaves Maria Regina D' Império-Lima José M Álvarez MyD88 activation in cardiomyocytes contributes to the heart immune response to acute Trypanosoma cruzi infection with no effect on local parasite control. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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, IFNγ and TNFα 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. |
format |
Article in Journal/Newspaper |
author |
Danni Yohani Santana Rafael Moysés Salgado Marina Fevereiro Rogério Silva do Nascimento Raissa Fonseca Niels Olsen Saraiva Câmara Sabrina Epiphanio Cláudio Romero Farias Marinho Maria Luiza Barreto-Chaves Maria Regina D' Império-Lima José M Álvarez |
author_facet |
Danni Yohani Santana Rafael Moysés Salgado Marina Fevereiro Rogério Silva do Nascimento Raissa Fonseca Niels Olsen Saraiva Câmara Sabrina Epiphanio Cláudio Romero Farias Marinho Maria Luiza Barreto-Chaves Maria Regina D' Império-Lima José M Álvarez |
author_sort |
Danni Yohani Santana |
title |
MyD88 activation in cardiomyocytes contributes to the heart immune response to acute Trypanosoma cruzi infection with no effect on local parasite control. |
title_short |
MyD88 activation in cardiomyocytes contributes to the heart immune response to acute Trypanosoma cruzi infection with no effect on local parasite control. |
title_full |
MyD88 activation in cardiomyocytes contributes to the heart immune response to acute Trypanosoma cruzi infection with no effect on local parasite control. |
title_fullStr |
MyD88 activation in cardiomyocytes contributes to the heart immune response to acute Trypanosoma cruzi infection with no effect on local parasite control. |
title_full_unstemmed |
MyD88 activation in cardiomyocytes contributes to the heart immune response to acute Trypanosoma cruzi infection with no effect on local parasite control. |
title_sort |
myd88 activation in cardiomyocytes contributes to the heart immune response to acute trypanosoma cruzi infection with no effect on local parasite control. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2018 |
url |
https://doi.org/10.1371/journal.pntd.0006617 https://doaj.org/article/6b89d81dc8f84510916bbbb27095f04b |
long_lat |
ENVELOPE(-112.453,-112.453,57.591,57.591) |
geographic |
Arctic The ''Y'' |
geographic_facet |
Arctic The ''Y'' |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 12, Iss 8, p e0006617 (2018) |
op_relation |
http://europepmc.org/articles/PMC6089445?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006617 https://doaj.org/article/6b89d81dc8f84510916bbbb27095f04b |
op_doi |
https://doi.org/10.1371/journal.pntd.0006617 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
12 |
container_issue |
8 |
container_start_page |
e0006617 |
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1766344178440077312 |