TY - JOUR
T1 - Tropism for tuft cells determines immune promotion of norovirus pathogenesis
AU - Wilen, Craig B.
AU - Lee, Sanghyun
AU - Hsieh, Leon L.
AU - Orchard, Robert C.
AU - Desai, Chandni
AU - Hykes, Barry L.
AU - McAllaster, Michael R.
AU - Balce, Dale R.
AU - Feehley, Taylor
AU - Brestoff, Jonathan R.
AU - Hickey, Christina A.
AU - Yokoyama, Christine C.
AU - Wang, Ya Ting
AU - MacDuff, Donna A.
AU - Kreamalmayer, Darren
AU - Howitt, Michael R.
AU - Neil, Jessica A.
AU - Cadwell, Ken
AU - Allen, Paul M.
AU - Handley, Scott A.
AU - van Lookeren Campagne, Menno
AU - Baldridge, Megan T.
AU - Virgin, Skip
N1 - Funding Information:
We acknowledge J. Guo, X. Zhang, A. Orvedahl, A. Mayer, T. Schaiff, M. Artyomov, G. Broze, and N. Lasky for helpful discussions and technical support. We also thank W. Beatty at the Molecular Microbiology Imaging Facility and E. Lantelme and D. Brinja at the Flow Cytometry Core at Washington University School of Medicine. Funding: This work was supported by NIH grants K08 AI128043 (C.B.W.); K22 AI127846 (M.T.B.); K99 DK116666 (R.C.O.); T32 AI007163 (C.C.Y.); R01 AI127552 and U19 AI109725 (H.W.V.); and DK093668, DK103788, HL123340, and R01 AI121244 (J.A.N. and K.C.). In addition, S.L. was supported by the Basic Sciences Research Program through the National Research Foundation of Korea, funded by the Ministry of Education (grant NRF-2016R1A6A3A03012352). M.T.B. was supported by Digestive Diseases Research Core Centers grant P30 DK052574. J.A.N. was supported by a Vilcek Fellowship and a Sir Keith Murdoch Fellowship.
Publisher Copyright:
2017 © The Authors
PY - 2018/4/13
Y1 - 2018/4/13
N2 - Complex interactions between host immunity and the microbiome regulate norovirus infection. However, the mechanism of host immune promotion of enteric virus infection remains obscure. The cellular tropism of noroviruses is also unknown. Recently, we identified CD300lf as a murine norovirus (MNoV) receptor. In this study, we have shown that tuft cells, a rare type of intestinal epithelial cell, express CD300lf and are the target cell for MNoV in the mouse intestine. We found that type 2 cytokines, which induce tuft cell proliferation, promote MNoV infection in vivo. These cytokines can replace the effect of commensal microbiota in promoting virus infection. Our work thus provides insight into how the immune system and microbes can coordinately promote enteric viral infection.
AB - Complex interactions between host immunity and the microbiome regulate norovirus infection. However, the mechanism of host immune promotion of enteric virus infection remains obscure. The cellular tropism of noroviruses is also unknown. Recently, we identified CD300lf as a murine norovirus (MNoV) receptor. In this study, we have shown that tuft cells, a rare type of intestinal epithelial cell, express CD300lf and are the target cell for MNoV in the mouse intestine. We found that type 2 cytokines, which induce tuft cell proliferation, promote MNoV infection in vivo. These cytokines can replace the effect of commensal microbiota in promoting virus infection. Our work thus provides insight into how the immune system and microbes can coordinately promote enteric viral infection.
UR - http://www.scopus.com/inward/record.url?scp=85045251077&partnerID=8YFLogxK
U2 - 10.1126/science.aar3799
DO - 10.1126/science.aar3799
M3 - Article
C2 - 29650672
AN - SCOPUS:85045251077
SN - 0036-8075
VL - 360
SP - 204
EP - 208
JO - Science
JF - Science
IS - 6385
ER -