IFN-I and IL-22 mediate protective effects of intestinal viral infection.
Animals
Anti-Bacterial Agents
/ toxicity
Cell Proliferation
Citrobacter rodentium
/ physiology
Colon
/ cytology
Dextran Sulfate
/ toxicity
Enterobacteriaceae Infections
/ prevention & control
Gastrointestinal Microbiome
/ immunology
Interferon Type I
/ metabolism
Interleukins
/ genetics
Intestinal Mucosa
/ cytology
Intestines
/ cytology
Lymphocytes
/ cytology
Mice, Inbred C57BL
Mice, Mutant Strains
Mutation
Norovirus
/ immunology
Signal Transduction
/ genetics
Specific Pathogen-Free Organisms
Viral Nonstructural Proteins
/ genetics
Virus Replication
Interleukin-22
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
11
07
2018
accepted:
26
04
2019
pmc-release:
10
12
2019
pubmed:
12
6
2019
medline:
21
1
2020
entrez:
12
6
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31182797
doi: 10.1038/s41564-019-0470-1
pii: 10.1038/s41564-019-0470-1
pmc: PMC6871771
mid: NIHMS1528073
doi:
Substances chimiques
Anti-Bacterial Agents
0
Interferon Type I
0
Interleukins
0
Viral Nonstructural Proteins
0
Dextran Sulfate
9042-14-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1737-1749Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK093668
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI130945
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI121244
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI100853
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK103788
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL123340
Pays : United States
Références
Cadwell, K. The virome in host health and disease. Immunity 42, 805–813 (2015).
doi: 10.1016/j.immuni.2015.05.003
Neil, J. A. & Cadwell, K. The intestinal virome and immunity. J. Immunol. 201, 1615–1624 (2018).
doi: 10.4049/jimmunol.1800631
Cadwell, K. et al. Virus-plus-susceptibility gene interaction determines Crohn’s disease gene Atg16L1 phenotypes in intestine. Cell 141, 1135–1145 (2010).
doi: 10.1016/j.cell.2010.05.009
Basic, M. et al. Norovirus triggered microbiota-driven mucosal inflammation in interleukin 10-deficient mice. Inflamm. Bowel Dis. 20, 431–443 (2014).
doi: 10.1097/01.MIB.0000441346.86827.ed
Seamons, A. et al. Obstructive lymphangitis precedes colitis in murine norovirus-infected Stat1-deficient mice. Am. J. Pathol. 188, 1536–1554 (2018).
doi: 10.1016/j.ajpath.2018.03.019
Cadwell, K. et al. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456, 259–263 (2008).
doi: 10.1038/nature07416
Matsuzawa-Ishimoto, Y. et al. Autophagy protein ATG16L1 prevents necroptosis in the intestinal epithelium. J. Exp. Med. 214, 3687–3705 (2017).
doi: 10.1084/jem.20170558
Kernbauer, E., Ding, Y. & Cadwell, K. An enteric virus can replace the beneficial function of commensal bacteria. Nature 516, 94–98 (2014).
doi: 10.1038/nature13960
Abt, M. C. et al. TLR-7 activation enhances IL-22-mediated colonization resistance against vancomycin-resistant enterococcus. Sci. Transl. Med. 8, 327ra325 (2016).
doi: 10.1126/scitranslmed.aad6663
Thepaut, M. et al. Protective role of murine norovirus against Pseudomonas aeruginosa acute pneumonia. Vet. Res. 46, 91 (2015).
doi: 10.1186/s13567-015-0239-3
Yang, J. Y. et al. Enteric viruses ameliorate gut inflammation via toll-like receptor 3 and toll-like receptor 7-mediated interferon-β production. Immunity 44, 889–900 (2016).
doi: 10.1016/j.immuni.2016.03.009
Vijay-Kumar, M. et al. Activation of toll-like receptor 3 protects against DSS-induced acute colitis. Inflamm. Bowel Dis. 13, 856–864 (2007).
doi: 10.1002/ibd.20142
Bailey, D., Thackray, L. B. & Goodfellow, I. G. A single amino acid substitution in the murine norovirus capsid protein is sufficient for attenuation in vivo. J. Virol. 82, 7725–7728 (2008).
doi: 10.1128/JVI.00237-08
Strong, D. W., Thackray, L. B., Smith, T. J. & Virgin, H. W. Protruding domain of capsid protein is necessary and sufficient to determine murine norovirus replication and pathogenesis in vivo. J. Virol. 86, 2950–2958 (2012).
doi: 10.1128/JVI.07038-11
Zhu, S. et al. Regulation of norovirus virulence by the VP1 protruding domain correlates with B cell infection efficiency. J. Virol. 90, 2858–2867 (2015).
doi: 10.1128/JVI.02880-15
Tomov, V. T. et al. Persistent enteric murine norovirus infection is associated with functionally suboptimal virus-specific CD8 T cell responses. J. Virol. 87, 7015–7031 (2013).
doi: 10.1128/JVI.03389-12
Nice, T. J., Strong, D. W., McCune, B. T., Pohl, C. S. & Virgin, H. W. A single-amino-acid change in murine norovirus NS1/2 is sufficient for colonic tropism and persistence. J. Virol. 87, 327–334 (2013).
doi: 10.1128/JVI.01864-12
Jones, M. K. et al. Enteric bacteria promote human and mouse norovirus infection of B cells. Science 346, 755–759 (2014).
doi: 10.1126/science.1257147
Baldridge, M. T. et al. Commensal microbes and interferon-λ determine persistence of enteric murine norovirus infection. Science 347, 266–269 (2015).
doi: 10.1126/science.1258025
Lee, S. et al. Norovirus cell tropism is determined by combinatorial action of a viral non-structural protein and host cytokine. Cell Host Microbe 22, 449–459 (2017).
doi: 10.1016/j.chom.2017.08.021
Wilen, C. B. et al. Tropism for tuft cells determines immune promotion of norovirus pathogenesis. Science 360, 204–208 (2018).
doi: 10.1126/science.aar3799
Sun, L. et al. Type I interferons link viral infection to enhanced epithelial turnover and repair. Cell Host Microbe 17, 85–97 (2015).
doi: 10.1016/j.chom.2014.11.004
McCartney, S. A. et al. MDA-5 recognition of a murine norovirus. PLoS Pathog. 4, e1000108 (2008).
doi: 10.1371/journal.ppat.1000108
Wang, P. et al. Nlrp6 regulates intestinal antiviral innate immunity. Science 350, 826–830 (2015).
doi: 10.1126/science.aab3145
MacDuff, D. A. et al. HOIL1 is essential for the induction of type I and III interferons by MDA5 and regulates persistent murine norovirus infection. J. Virol. 92, e01368-18 (2018).
doi: 10.1128/JVI.01368-18
Pickert, G. et al. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J. Exp. Med. 206, 1465–1472 (2009).
doi: 10.1084/jem.20082683
Seo, S. U. et al. Intestinal macrophages arising from CCR2
doi: 10.1038/ncomms9010
Tschurtschenthaler, M. et al. Type I interferon signalling in the intestinal epithelium affects Paneth cells, microbial ecology and epithelial regeneration. Gut 63, 1921–1931 (2014).
doi: 10.1136/gutjnl-2013-305863
Pott, J. et al. IFN-λ determines the intestinal epithelial antiviral host defense. Proc. Natl Acad. Sci. USA 108, 7944–7949 (2011).
doi: 10.1073/pnas.1100552108
Baldridge, M. T. et al. Expression of Ifnlr1 on intestinal epithelial cells is critical to the antiviral effects of interferon lambda against norovirus and reovirus. J. Virol. 91, e02079-02016 (2017).
doi: 10.1128/JVI.02079-16
Nice, T. J. et al. Interferon-λ cures persistent murine norovirus infection in the absence of adaptive immunity. Science 347, 269–273 (2015).
doi: 10.1126/science.1258100
Gronke, K. et al. Interleukin-22 protects intestinal stem cells against genotoxic stress. Nature 566, 249–253 (2019).
doi: 10.1038/s41586-019-0899-7
Lim, E. S. et al. Early life dynamics of the human gut virome and bacterial microbiome in infants. Nat. Med. 21, 1228–1234 (2015).
doi: 10.1038/nm.3950
Mao, K. et al. Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism. Nature 554, 255–259 (2018).
doi: 10.1038/nature25437
Zheng, Y. et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat. Med. 14, 282–289 (2008).
doi: 10.1038/nm1720
Kim, Y. G. et al. Neonatal acquisition of Clostridia species protects against colonization by bacterial pathogens. Science 356, 315–319 (2017).
doi: 10.1126/science.aag2029
Ettayebi, K. & Hardy, M. E. Norwalk virus nonstructural protein p48 forms a complex with the SNARE regulator VAP-A and prevents cell surface expression of vesicular stomatitis virus G protein. J. Virol. 77, 11790–11797 (2003).
doi: 10.1128/JVI.77.21.11790-11797.2003
Fernandez-Vega, V. et al. Norwalk virus N-terminal nonstructural protein is associated with disassembly of the Golgi complex in transfected cells. J. Virol. 78, 4827–4837 (2004).
doi: 10.1128/JVI.78.9.4827-4837.2004
McCune, B. T. et al. Noroviruses co-opt the function of host proteins VAPA and VAPB for replication via a phenylalanine-phenylalanine-acidic-tract-motif mimic in nonstructural viral protein NS1/2. mBio 8, e00668-17 (2017).
doi: 10.1128/mBio.00668-17
Baker, E. S. et al. Inherent structural disorder and dimerisation of murine norovirus NS1-2 protein. PLoS ONE 7, e30534 (2012).
doi: 10.1371/journal.pone.0030534
Broggi, A., Tan, Y., Granucci, F. & Zanoni, I. IFN-λ suppresses intestinal inflammation by non-translational regulation of neutrophil function. Nat. Immunol. 18, 1084–1093 (2017).
doi: 10.1038/ni.3821
Martin, P. K. et al. Autophagy proteins suppress protective type I interferon signalling in response to the murine gut microbiota. Nat. Microbiol. 3, 1131–1141 (2018).
doi: 10.1038/s41564-018-0229-0
Van Winkle, J. A. et al. Persistence of systemic murine norovirus is maintained by inflammatory recruitment of susceptible myeloid cells. Cell Host Microbe 24, 665–676 (2018).
doi: 10.1016/j.chom.2018.10.003
Phillips, G., Tam, C. C., Rodrigues, L. C. & Lopman, B. Prevalence and characteristics of asymptomatic norovirus infection in the community in England. Epidemiol. Infect. 138, 1454–1458 (2010).
doi: 10.1017/S0950268810000439
Bouziat, R. et al. Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science 356, 44–50 (2017).
doi: 10.1126/science.aah5298
Bouziat, R. et al. Murine norovirus infection induces T
doi: 10.1016/j.chom.2018.10.004
Caporaso, J. G. et al. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods 7, 335–336 (2010).
doi: 10.1038/nmeth.f.303
Chen, J. et al. Associating microbiome composition with environmental covariates using generalized UniFrac distances. Bioinformatics 28, 2106–2113 (2012).
doi: 10.1093/bioinformatics/bts342
Lozupone, C., Lladser, M. E., Knights, D., Stombaugh, J. & Knight, R. UniFrac: an effective distance metric for microbial community comparison. ISME J. 5, 169–172 (2011).
doi: 10.1038/ismej.2010.133
Vazquez-Baeza, Y., Pirrung, M., Gonzalez, A. & Knight, R. EMPeror: a tool for visualizing high-throughput microbial community data. Gigascience 2, 16 (2013).
doi: 10.1186/2047-217X-2-16