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Recent studies indicate that certain TLRs activate immunological autophagy to eliminate microbes. It remains unknown whether TLRs regulate autophagy to play a role in the heart. This study examined this question. The activation of TLR3 in cultured cardiomyocytes was observed to increase protein levels of autophagic components, including LC3\u2010II, a specific marker for autophagy induction, and p62\/SQSTM1, an autophagy receptor normally degraded in the final step of autophagy. The results of transfection with a tandem mRFP\u2010GFP\u2010LC3 adenovirus and use of an autophagic flux inhibitor chloroquine both suggested that TLR3 in cardiomyocytes promotes autophagy induction without affecting autophagic flux. Gene\u2010knockdown experiments showed that the TRIF\u2010dependent pathway mediated the autophagic effect of TLR3. In the mouse model of chronic myocardial infarction, persistent autophagy was observed, concomitant with up\u2010regulated TLR3 expression and increased TLR3\u2010Trif signalling. Germline knockout (KO) of TLR3 inhibited autophagy, reduced infarct size, attenuated heart failure and improved survival. These protective effects were abolished by <jats:italic>in\u00a0vivo<\/jats:italic> administration of an autophagy inducer rapamycin. Similar to the results obtained in cultured cardiomyocytes, TLR3\u2010KO did not prevent autophagic flux in mouse heart. Additionally, this study failed to detect the involvement of inflammation in TLR3\u2010KO\u2010derived protection, as wild\u2010type and TLR3\u2010KO hearts were comparable in inflammatory activity. It is concluded that up\u2010regulated TLR3 expression and signalling contributes to persistent autophagy following MI, which promotes heart failure and lethality.<\/jats:p>","DOI":"10.1111\/jcmm.13328","type":"journal-article","created":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T10:29:22Z","timestamp":1506335362000},"page":"395-408","source":"Crossref","is-referenced-by-count":39,"title":["TLR3 contributes to persistent autophagy and heart failure in mice after myocardial infarction"],"prefix":"10.1111","volume":"22","author":[{"given":"Ting","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Physiology and Key Lab of Ministry of Education in Fertility Preservation and Maintenance Ningxia Medical University Yinchuan China"},{"name":"Department of Physiology Shanghai Jiao Tong University School of Medicine Shanghai 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