The Journal of Experimental Medicine
Keystone Symposia
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Published online May 14, 2007
doi:10.1084/jem.20061587
The Journal of Experimental Medicine, Vol. 204, No. 6, 1349-1358
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Johansson et al.
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ARTICLE

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

Cecilia Johansson1, J. Denise Wetzel2,3, JianPing He1, Carmen Mikacenic1, Terence S. Dermody2,3,4, and Brian L. Kelsall1

1 Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
2 Department of Pediatrics, 4 Department of Microbiology and Immunology, and 3 Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN 37232

CORRESPONDENCE Brian L. Kelsall: kelsall{at}nih.gov OR Terence S. Dermody: terry.dermody{at}vanderbilt.edu

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-ß, and Mx-1 in PPs and caused localized intestinal infection that was cleared in 10 d. In contrast, T1L produced fatal systemic infection in IFN{alpha}R1 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.

Abbreviations used: Ab, antibody; cDC, conventional DC; FAE, follicular-associated epithelium; ISG, IFN-stimulated gene; Mda, melanoma differentiation-associated gene; MLN, mesenteric LN; pDC, plasmacytoid DC; PKR, protein kinase dependent on RNA; PP, Peyer's patch; RIG-I, retinoic acid–inducible gene; T1L, type 1 Lang; TLR, Toll-like receptor.

C. Johansson's present address is Dept. of Respiratory Medicine, National Heart and Lung Institute, Imperial College, London, W2 1PG, England, UK.


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