TY - JOUR
T1 - IFN-I and IL-22 mediate protective effects of intestinal viral infection
AU - Neil, Jessica A.
AU - Matsuzawa-Ishimoto, Yu
AU - Kernbauer-Hölzl, Elisabeth
AU - Schuster, Samantha L.
AU - Sota, Stela
AU - Venzon, Mericien
AU - Dallari, Simone
AU - Galvao Neto, Antonio
AU - Hine, Ashley
AU - Hudesman, David
AU - Loke, P’ng
AU - Nice, Timothy J.
AU - Cadwell, Ken
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Products derived from bacterial members of the gut microbiota evoke immune signalling pathways of the host that promote immunity and barrier function in the intestine. How immune reactions to enteric viruses support intestinal homeostasis is unknown. We recently demonstrated that infection by murine norovirus (MNV) reverses intestinal abnormalities following depletion of bacteria, indicating that an intestinal animal virus can provide cues to the host that are typically attributed to the microbiota. Here, we elucidate mechanisms by which MNV evokes protective responses from the host. We identify an important role for the viral protein NS1/2 in establishing local replication and a type I interferon (IFN-I) response in the colon. We further show that IFN-I acts on intestinal epithelial cells to increase the proportion of CCR2-dependent macrophages and interleukin (IL)-22-producing innate lymphoid cells, which in turn promote pSTAT3 signalling in intestinal epithelial cells and protection from intestinal injury. In addition, we demonstrate that MNV provides a striking IL-22-dependent protection against early-life lethal infection by Citrobacter rodentium. These findings demonstrate novel ways in which a viral member of the microbiota fortifies the intestinal barrier during chemical injury and infectious challenges.
AB - Products derived from bacterial members of the gut microbiota evoke immune signalling pathways of the host that promote immunity and barrier function in the intestine. How immune reactions to enteric viruses support intestinal homeostasis is unknown. We recently demonstrated that infection by murine norovirus (MNV) reverses intestinal abnormalities following depletion of bacteria, indicating that an intestinal animal virus can provide cues to the host that are typically attributed to the microbiota. Here, we elucidate mechanisms by which MNV evokes protective responses from the host. We identify an important role for the viral protein NS1/2 in establishing local replication and a type I interferon (IFN-I) response in the colon. We further show that IFN-I acts on intestinal epithelial cells to increase the proportion of CCR2-dependent macrophages and interleukin (IL)-22-producing innate lymphoid cells, which in turn promote pSTAT3 signalling in intestinal epithelial cells and protection from intestinal injury. In addition, we demonstrate that MNV provides a striking IL-22-dependent protection against early-life lethal infection by Citrobacter rodentium. These findings demonstrate novel ways in which a viral member of the microbiota fortifies the intestinal barrier during chemical injury and infectious challenges.
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UR - http://www.scopus.com/inward/citedby.url?scp=85067066317&partnerID=8YFLogxK
U2 - 10.1038/s41564-019-0470-1
DO - 10.1038/s41564-019-0470-1
M3 - Article
C2 - 31182797
AN - SCOPUS:85067066317
SN - 2058-5276
VL - 4
SP - 1737
EP - 1749
JO - Nature Microbiology
JF - Nature Microbiology
IS - 10
ER -