PMID- 17502662 OWN - NLM STAT- MEDLINE DCOM- 20071213 LR - 20230507 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 204 IP - 6 DP - 2007 Jun 11 TI - Type I interferons produced by hematopoietic cells protect mice against lethal infection by mammalian reovirus. PG - 1349-58 AB - We defined the function of type I interferons (IFNs) in defense against reovirus strain type 1 Lang (T1L), which is a double-stranded RNA virus that infects Peyer's patches (PPs) after peroral inoculation of mice. T1L induced expression of mRNA for IFN-alpha, IFN-beta, and Mx-1 in PPs and caused localized intestinal infection that was cleared in 10 d. In contrast, T1L produced fatal systemic infection in IFNalphaR1 knockout (KO) mice with extensive cell loss in lymphoid tissues and necrosis of the intestinal mucosa. Studies of bone-marrow chimeric mice indicated an essential role for hematopoietic cells in IFN-dependent viral clearance. Dendritic cells (DCs), including conventional DCs (cDCs), were the major source of type I IFNs in PPs of reovirus-infected mice, whereas all cell types expressed the antiviral protein Mx-1. Neither NK cells nor signaling via Toll-like receptor 3 or MyD88 were essential for viral clearance. These data demonstrate a requirement for type I IFNs in the control of an intestinal viral infection and indicate that cDCs are a significant source of type I IFN production in vivo. Therefore, innate immunity in PPs is an essential component of host defense that limits systemic spread of pathogens that infect the intestinal mucosa. FAU - Johansson, Cecilia AU - Johansson C AD - Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Wetzel, J Denise AU - Wetzel JD FAU - He, Jianping AU - He J FAU - Mikacenic, Carmen AU - Mikacenic C FAU - Dermody, Terence S AU - Dermody TS FAU - Kelsall, Brian L AU - Kelsall BL LA - eng GR - P30 DK020593/DK/NIDDK NIH HHS/United States GR - P30 CA068485/CA/NCI NIH HHS/United States GR - AI50080/AI/NIAID NIH HHS/United States GR - DK20593/DK/NIDDK NIH HHS/United States GR - CA68485/CA/NCI NIH HHS/United States GR - R01 AI050080/AI/NIAID NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20070514 PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Interferon Type I) SB - IM MH - Animals MH - Bone Marrow Cells/*immunology MH - Dendritic Cells/*immunology MH - Immunohistochemistry MH - Interferon Type I/genetics/*immunology/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Orthoreovirus, Mammalian/*immunology MH - Peyer's Patches/*immunology/virology MH - Reoviridae Infections/immunology/*prevention & control MH - Reverse Transcriptase Polymerase Chain Reaction MH - Survival Analysis PMC - PMC2118611 EDAT- 2007/05/16 09:00 MHDA- 2007/12/14 09:00 PMCR- 2007/12/11 CRDT- 2007/05/16 09:00 PHST- 2007/05/16 09:00 [pubmed] PHST- 2007/12/14 09:00 [medline] PHST- 2007/05/16 09:00 [entrez] PHST- 2007/12/11 00:00 [pmc-release] AID - jem.20061587 [pii] AID - 20061587 [pii] AID - 10.1084/jem.20061587 [doi] PST - ppublish SO - J Exp Med. 2007 Jun 11;204(6):1349-58. doi: 10.1084/jem.20061587. Epub 2007 May 14.