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. HandleyMenno van Lookeren Campagne, Megan T. Baldridge, Herbert W. Virgin

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)204-208
Number of pages5
JournalScience
Volume360
Issue number6385
DOIs
StatePublished - Apr 13 2018
Externally publishedYes

ASJC Scopus subject areas

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    Wilen, C. B., Lee, S., Hsieh, L. L., Orchard, R. C., Desai, C., Hykes, B. L., McAllaster, M. R., Balce, D. R., Feehley, T., Brestoff, J. R., Hickey, C. A., Yokoyama, C. C., Wang, Y. T., MacDuff, D. A., Kreamalmayer, D., Howitt, M. R., Neil, J. A., Cadwell, K., Allen, P. M., ... Virgin, H. W. (2018). Tropism for tuft cells determines immune promotion of norovirus pathogenesis. Science, 360(6385), 204-208. https://doi.org/10.1126/science.aar3799