title: Protection against type 1 diabetes upon Coxsackievirus B4 infection and iNKT-cell stimulation: role of suppressive macrophages.
abstract: Invariant natural killer T (iNKT) cells belong to the innate immune system and exercise a dual role as potent regulators of autoimmunity and participate in responses against different pathogens. They have been shown to prevent type 1 diabetes development and to promote antiviral responses. Many studies in the implication of environmental factors on the etiology of type 1 diabetes have suggested a link between enteroviral infections and the development of this disease. This study of the pancreatropic enterovirus Coxsackievirus B4 (CVB4) shows that although infection accelerated type 1 diabetes development in a subset of proinsulin 2-deficient NOD mice, the activation of iNKT cells by a specific agonist, α-galactosylceramide, at the time of infection inhibited the disease. Diabetes development was associated with the infiltration of pancreatic islets by inflammatory macrophages, producing high levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α and activation of anti-islet T cells. On the contrary, macrophages infiltrating the islets after CVB4 infection and iNKT-cell stimulation expressed a number of suppressive enzymes, among which indoleamine 2,3-dioxygenase was sufficient to inhibit anti-islet T-cell response and to prevent diabetes. This study highlights the critical interaction between virus and the immune system in the acceleration or prevention of type 1 diabetes.
authors.affiliation: INSERM U1016, Hospital Cochin/St. Vincent de Paul, Paris, France.
authors.forename: Liana
authors.initials: L
authors.lastname: Ghazarian
authors.forename: Julien
authors.initials: J
authors.lastname: Diana
authors.forename: Lucie
authors.initials: L
authors.lastname: Beaudoin
authors.forename: Pär G
authors.initials: PG
authors.lastname: Larsson
authors.forename: Raj K
authors.initials: RK
authors.lastname: Puri
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Malin
authors.initials: M
authors.lastname: Flodström-Tullberg
authors.forename: Agnès
authors.initials: A
authors.lastname: Lehuen
mesh_terms: D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology; D018793:Interleukin-13 / Q000502:physiology; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D005699:Galactosylceramides; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018793:Interleukin-13; C493154:alpha-galactosylceramide; D007371:Interferon-gamma
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