Hartman Institute for Therapeutic Organ Regeneration

Cardiomyocytes recruit monocytes upon SARS-CoV-2 infection by secreting CCL2.

TitleCardiomyocytes recruit monocytes upon SARS-CoV-2 infection by secreting CCL2.
Publication TypeJournal Article
Year of Publication2021
AuthorsYang L, Nilsson-Payant BE, Han Y, Jaffré F, Zhu J, Wang P, Zhang T, Redmond D, Houghton S, Møller R, Hoagland D, Carrau L, Horiuchi S, Goff M, Lim JK, Bram Y, Richardson C, Chandar V, Borczuk A, Huang Y, Xiang J, Ho DD, Schwartz RE, tenOever BR, Evans T, Chen S
JournalStem Cell Reports
Volume16
Issue9
Pagination2274-2288
Date Published2021 Sep 14
ISSN2213-6711
KeywordsAnimals, Cell Communication, Cell Line, Chemokine CCL2, Chlorocebus aethiops, COVID-19, Cricetinae, Disease Models, Animal, Heart Injuries, Humans, Macrophages, Male, Monocytes, Myocytes, Cardiac, Pluripotent Stem Cells, Vero Cells
Abstract

<p>Heart injury has been reported in up to 20% of COVID-19 patients, yet the cause of myocardial histopathology remains unknown. Here, using an established in vivo hamster model, we demonstrate that SARS-CoV-2 can be detected in cardiomyocytes of infected animals. Furthermore, we found damaged cardiomyocytes in hamsters and COVID-19 autopsy samples. To explore the mechanism, we show that both human pluripotent stem cell-derived cardiomyocytes (hPSC-derived CMs) and adult cardiomyocytes (CMs) can be productively infected by SARS-CoV-2, leading to secretion of the monocyte chemoattractant cytokine CCL2 and subsequent monocyte recruitment. Increased CCL2 expression and monocyte infiltration was also observed in the hearts of infected hamsters. Although infected CMs suffer damage, we find that the presence of macrophages significantly reduces SARS-CoV-2-infected CMs. Overall, our study provides direct evidence that SARS-CoV-2 infects CMs in vivo and suggests a mechanism of immune cell infiltration and histopathology in heart tissues of COVID-19 patients.</p>

DOI10.1016/j.stemcr.2021.07.012
Alternate JournalStem Cell Reports
PubMed ID34403650
PubMed Central IDPMC8289700
Grant ListR01 DK130454 / DK / NIDDK NIH HHS / United States
R35 HL135778 / HL / NHLBI NIH HHS / United States
R01 DK119667 / DK / NIDDK NIH HHS / United States
R01 CA234614 / CA / NCI NIH HHS / United States
R01 DK124463 / DK / NIDDK NIH HHS / United States
U01 DK127777 / DK / NIDDK NIH HHS / United States
R03 DK117252 / DK / NIDDK NIH HHS / United States
R01 DK116075 / DK / NIDDK NIH HHS / United States
/ AHA / American Heart Association-American Stroke Association / United States
R01 DK121072 / DK / NIDDK NIH HHS / United States
R01 AI107301 / AI / NIAID NIH HHS / United States

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Hartman Institute for Therapeutic Organ Regeneration
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