Type I interferons produced by hematopoietic cells protect mice against lethal infection by mammalian reovirus.
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.
Johansson
Cecilia
C
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Wetzel
J Denise
JD
He
Jianping
J
Mikacenic
Carmen
C
Dermody
Terence S
TS
Kelsall
Brian L
BL
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D030102:Orthoreovirus, Mammalian / Q000276:immunology*; D010581:Peyer's Patches / Q000276:immunology* / Q000821:virology; D012088:Reoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D007370:Interferon Type I