title: Nasal cardiac myosin peptide treatment and OX40 blockade protect mice from acute and chronic virally-induced myocarditis.
abstract: Myocarditis poses a severe health problem, can lead to dilated cardiomyopathy (DCM) and death, and is thought to be triggered by infections. Enteroviruses such as Coxsackie virus B3 (CVB3) have been implicated as a culprit, since they can cause acute and chronic heart disease in susceptible mice. CVB was detected in human cardiac myocytes in some cases, whereas acute CVB infection was thought to have caused death. Here we studied, whether nasal administration of cardiac myosin (CM) major histocompatibility class (MHC) II peptides CM₉₄₇-₉₆₀ and CM₇₃₅-₇₄₇ and OX40 blockade would be able to ameliorate immunopathology and heart disease in BALB/C mice infected with CVB3. We found that nasal CM-peptide prophylactic treatment significantly reduced myocarditis and mortality by enhancing Treg and IL-10 induction and that blockade of OX40 signaling could reduce heart inflammation when administered late during pathogenesis. Altogether, these results chart the way for novel prevention and intervention strategies for viral myocarditis.
authors.affiliation: Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Georgia
authors.initials: G
authors.lastname: Fousteri
authors.forename: Amy
authors.initials: A
authors.lastname: Dave
authors.forename: Bret
authors.initials: B
authors.lastname: Morin
authors.forename: Shaida
authors.initials: S
authors.lastname: Omid
authors.forename: Michael
authors.initials: M
authors.lastname: Croft
authors.forename: Matthias G
authors.initials: MG
authors.lastname: von Herrath
mesh_terms: D000208:Acute Disease; D000281:Administration, Intranasal; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D024722:Cardiac Myosins / Q000008:administration & dosage*; D002908:Chronic Disease; D003384:Coxsackievirus Infections / Q000276:immunology / Q000517:prevention & control*; D029822:Enterovirus B, Human; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology / Q000517:prevention & control*; D053262:Receptors, OX40 / Q000037:antagonists & inhibitors*; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse; D016753:Interleukin-10; D024722:Cardiac Myosins