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; Menno van Lookeren Campagne; Megan T. Baldridge; Herbert W. Virgin

doi:10.1126/science.aar3799

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 journal › Article › peer-review

153 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 language	English (US)
Pages (from-to)	204-208
Number of pages	5
Journal	Science
Volume	360
Issue number	6385
DOIs	https://doi.org/10.1126/science.aar3799
State	Published - Apr 13 2018
Externally published	Yes

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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

Wilen, CB, Lee, S, Hsieh, LL, Orchard, RC, Desai, C, Hykes, BL, McAllaster, MR, Balce, DR, Feehley, T, Brestoff, JR, Hickey, CA, Yokoyama, CC, Wang, YT, MacDuff, DA, Kreamalmayer, D, Howitt, MR, Neil, JA, Cadwell, K, Allen, PM, Handley, SA, van Lookeren Campagne, M, Baldridge, MT & Virgin, HW 2018, 'Tropism for tuft cells determines immune promotion of norovirus pathogenesis', Science, vol. 360, no. 6385, pp. 204-208. https://doi.org/10.1126/science.aar3799

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title = "Tropism for tuft cells determines immune promotion of norovirus pathogenesis",

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.",

author = "Wilen, {Craig B.} and Sanghyun Lee and Hsieh, {Leon L.} and Orchard, {Robert C.} and Chandni Desai and Hykes, {Barry L.} and McAllaster, {Michael R.} and Balce, {Dale R.} and Taylor Feehley and Brestoff, {Jonathan R.} and Hickey, {Christina A.} and Yokoyama, {Christine C.} and Wang, {Ya Ting} and MacDuff, {Donna A.} and Darren Kreamalmayer and Howitt, {Michael R.} and Neil, {Jessica A.} and Ken Cadwell and Allen, {Paul M.} and Handley, {Scott A.} and {van Lookeren Campagne}, Menno and Baldridge, {Megan T.} and Virgin, {Herbert W.}",

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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, Herbert W.

PY - 2018/4/13

Y1 - 2018/4/13

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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.

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Tropism for tuft cells determines immune promotion of norovirus pathogenesis

Abstract

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