Tropism for tuft cells determines immune promotion of norovirus pathogenesis
Craig B Wilen, Sanghyun Lee, Leon L Hsieh, Robert C Orchard, Chandni Desai, Barry L Hykes, Michael R McAllaster, Dale R Balce, Taylor Feehley, Jonathan R Brestoff, Christina A Hickey, Christine C Yokoyama, Ya-Ting Wang, Donna A MacDuff, Darren Kreamalmayer, Michael R Howitt, Jessica A Neil, Ken Cadwell, Paul M Allen, Scott A Handley Show all
Science | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2018
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..View full abstract
Awarded by NIH
Awarded by National Research Foundation of Korea - Ministry of Education
Awarded by Digestive Diseases Research Core Centers grant
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.