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Endogenous ligands for Toll\u2010like receptor 2 (<jats:styled-content style=\"fixed-case\">TLR2<\/jats:styled-content>) are released by damaged tissues and might play an important role in activating the innate immune system following muscle injury. To test this hypothesis, we compared macrophage behaviour and muscle repair mechanisms in mice lacking <jats:styled-content style=\"fixed-case\">TLR2<\/jats:styled-content> under conditions of either acute (cardiotoxin\u2010induced) or chronic (mdx mouse genetic model of Duchenne muscular dystrophy; <jats:styled-content style=\"fixed-case\">DMD<\/jats:styled-content>) muscle damage. In previously healthy muscle subjected to acute damage, <jats:styled-content style=\"fixed-case\">TLR2<\/jats:styled-content> deficiency reduced macrophage numbers in the muscle post\u2010injury but did not alter the expression pattern of the prototypical macrophage polarization markers <jats:styled-content style=\"fixed-case\">iNOS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CD206<\/jats:styled-content>. In addition, there was abnormal persistence of necrotic fibres and impaired regeneration in <jats:styled-content style=\"fixed-case\">TLR2<\/jats:styled-content>\u2212\/\u2212 muscles after acute injury. In\u00a0contrast, <jats:styled-content style=\"fixed-case\">TLR2<\/jats:styled-content> ablation in chronically diseased muscles of mdx mice not only resulted in significantly reduced macrophage numbers but additionally modified their phenotype by shifting from inflammatory (<jats:styled-content style=\"fixed-case\">iNOS<jats:sup>pos<\/jats:sup>CD206<jats:sup>neg<\/jats:sup><\/jats:styled-content>) to more anti\u2010inflammatory (<jats:styled-content style=\"fixed-case\">iNOS<jats:sup>neg<\/jats:sup>CD206<jats:sup>pos<\/jats:sup><\/jats:styled-content>) characteristics. This decrease in macrophage\u2010mediated inflammation was associated with ameliorated muscle histopathology and improved force\u2010generating capacity of the dystrophic muscle. Our results suggest that the role of <jats:styled-content style=\"fixed-case\">TLR2<\/jats:styled-content> in macrophage function and skeletal muscle repair depends greatly upon the muscle injury context, and raise the possibility that inhibition of <jats:styled-content style=\"fixed-case\">TLR2<\/jats:styled-content> could serve as a useful therapeutic measure in <jats:styled-content style=\"fixed-case\">DMD<\/jats:styled-content>. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4689","type":"journal-article","created":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T08:49:50Z","timestamp":1453452590000},"page":"10-22","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Divergent impact of Toll\u2010like receptor 2 deficiency on repair mechanisms in healthy muscle versus Duchenne muscular dystrophy"],"prefix":"10.1002","volume":"239","author":[{"given":"Kamalika","family":"Mojumdar","sequence":"first","affiliation":[{"name":"Meakins\u2010Christie Laboratories and Program for Translational Research in Respiratory Diseases McGill University Health Centre Research Institute  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Giordano","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories and Program for Translational Research in 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