title: Macrophages and galectin 3 play critical roles in CVB3-induced murine acute myocarditis and chronic fibrosis.
abstract: Macrophage influx and galectin 3 production have been suggested as major players driving acute inflammation and chronic fibrosis in many diseases. However, their involvement in the pathogenesis of viral myocarditis and subsequent cardiomyopathy are unknown. Our aim was to characterise the role of macrophages and galectin 3 on survival, clinical course, viral burden, acute pathology, and chronic fibrosis in coxsackievirus B3 (CVB3)-induced myocarditis. Our results showed that C3H/HeJ mice infected with CVB3 and depleted of macrophages by liposome-encapsulated clodronate treatment compared with infected untreated mice presented higher viral titres but reduced acute myocarditis and chronic fibrosis, compared with untreated infected mice. Increased galectin 3 transcriptional and translational expression levels correlated with CVB3 infection in macrophages and in non-depleted mice. Disruption of the galectin 3 gene did not affect viral titres but reduced acute myocarditis and chronic fibrosis compared with C57BL/6J wild-type mice. Similar results were observed after pharmacological inhibition of galectin 3 with N-acetyl-d-lactosamine in C3H/HeJ mice. Our results showed a critical role of macrophages and their galectin 3 in controlling acute viral-induced cardiac injury and the subsequent fibrosis. Moreover, the fact that pharmacological inhibition of galectin 3 induced similar results to macrophage depletion regarding the degree of acute cardiac inflammation and chronic fibrosis opens up the possibility of new pharmacological strategies for viral myocarditis.
authors.affiliation: Instituto de Biotecnología y Biología Molecular, CONICET-UNLP, La Plata, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Jaquenod De Giusti
authors.affiliation: Instituto de Biotecnología y Biología Molecular, CONICET-UNLP, La Plata, Argentina.
authors.forename: Agustín E
authors.initials: AE
authors.lastname: Ure
authors.affiliation: Instituto de Medicina Experimental, CONICET-ANM, Argentina.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Rivadeneyra
authors.affiliation: Instituto de Medicina Experimental, CONICET-ANM, Argentina.
authors.forename: Mirta
authors.initials: M
authors.lastname: Schattner
authors.affiliation: Instituto de Biotecnología y Biología Molecular, CONICET-UNLP, La Plata, Argentina. Electronic address: rmg1426@gmail.com.
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Gomez
mesh_terms: D000818:Animals; D002460:Cell Line; D003384:Coxsackievirus Infections / Q000150:complications*; D004770:Enterovirus; D005355:Fibrosis; D037502:Galectin 3 / Q000502:physiology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009205:Myocarditis / Q000276:immunology* / Q000378:metabolism / Q000821:virology
chemical_list: D037502:Galectin 3
keywords: Coxsackievirus B3; Fibrosis; Galectin 3; Macrophages; Myocarditis