title: Innate immune responses to rotavirus infection in macrophages depend on MAVS but involve neither the NLRP3 inflammasome nor JNK and p38 signaling pathways.
abstract: Rotavirus infection is a major cause of life-threatening infantile gastroenteritis. The innate immune system provides an immediate mechanism of suppressing viral replication and is necessary for an effective adaptive immune response. Innate immunity involves host recognition of viral infection and establishment of a powerful antiviral state through the expression of pro-inflammatory cytokines such as type-1 interferon (IFN). Macrophages, the front-line cells of innate immunity, produce IFN and other cytokines in response to viral infection. However, the role of macrophages during rotavirus infection is not well defined. We demonstrate here that RRV rotavirus triggers the production of proinflammatory cytokines from mouse bone marrow-derived macrophages. IFN and antiviral cytokine production was abolished in rotavirus-infected MAVS (-/-) macrophages. This indicates that rotavirus triggers innate immunity in macrophages through RIG-I and/or MDA5 viral recognition, and MAVS signaling is essential for cytokine responses in macrophages. Rotavirus induced IFN expression in both wild type and MDA5 (-/-) macrophages, showing that MDA5 is not essential for IFN secretion following infection, and RIG-I and MDA5 may act redundantly in promoting rotavirus recognition. Interestingly, rotavirus neither stimulated mitogen-activated protein kinases p38 and JNK nor activated the NLRP3 inflammasome, demonstrating that these components might not be involved in innate responses to rotavirus infection in macrophages. Our results indicate that rotavirus elicits intracellular signaling in macrophages, resulting in the induction of IFN and antiviral cytokines, and advance our understanding of the involvement of these cells in innate responses against rotavirus.
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, Victoria 3000, Australia.
authors.forename: Izabel J M
authors.initials: IJ
authors.lastname: Di Fiore
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, Victoria 3000, Australia.
authors.forename: Gavan
authors.initials: G
authors.lastname: Holloway
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, Victoria 3000, Australia. Electronic address: barbarac@unimelb.edu.au.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Coulson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012401:Rotavirus / Q000276:immunology / Q000502:physiology*; D012400:Rotavirus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D058847:Inflammasomes; D048670:MAP Kinase Kinase 4; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D048051:p38 Mitogen-Activated Protein Kinases; C512612:MAVS protein, mouse; C492716:Nlrp3 protein, mouse
keywords: Inflammasome; Innate immune responses; Macrophages; Pattern recognition receptors; Rotavirus