Type I interferons produced by hematopoietic cells protect mice against lethal infection by mammalian reovirus.

Title: Type I interferons produced by hematopoietic cells protect mice against lethal infection by mammalian reovirus.
Authors: Johansson, C
Wetzel, JD
He, J
Mikacenic, C
Dermody, TS
Kelsall, BL
Item Type: Journal Article
Abstract: 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 Peyers 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.
Issue Date: 11-Jun-2007
URI: http://hdl.handle.net/10044/1/18609
DOI: http://dx.doi.org/10.1084/jem.20061587
ISSN: 0022-1007
Start Page: 1349
End Page: 1358
Journal / Book Title: J Exp Med
Volume: 204
Issue: 6
Copyright Statement: © 2007 Rockefeller University Press. Six months after publication, third parties (that is, anyone who is not an author) can use the material we publish under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Conference Place: United States
Appears in Collections:National Heart and Lung Institute



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