Virus infection is controlled by hematopoietic and stromal cell sensing of murine cytomegalovirus through sting

Sytse J. Piersma; Jennifer Poursine-Laurent; Liping Yang; Glen N. Barber; Bijal A. Parikh; Wayne M. Yokoyama

doi:10.7554/eLife.56882

Virus infection is controlled by hematopoietic and stromal cell sensing of murine cytomegalovirus through sting

Sytse J. Piersma, Jennifer Poursine-Laurent, Liping Yang, Glen N. Barber, Bijal A. Parikh, Wayne M. Yokoyama

Cell Biology

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Recognition of DNA viruses, such as cytomegaloviruses (CMVs), through pattern-recognition receptor (PRR) pathways involving MyD88 or STING constitute a first-line defense against infections mainly through production of type I interferon (IFN-I). However, the role of these pathways in different tissues is incompletely understood, an issue particularly relevant to the CMVs which have broad tissue tropisms. Herein, we contrasted anti-viral effects of MyD88 versus STING in distinct cell types that are infected with murine CMV (MCMV). Bone marrow chimeras revealed STING-mediated MCMV control in hematological cells, similar to MyD88. However, unlike MyD88, STING also contributed to viral control in non-hematological, stromal cells. Infected splenic stromal cells produced IFN-I in a cGAS-STING-dependent and MyD88-independent manner, while we confirmed plasmacytoid dendritic cell IFN-I had inverse requirements. MCMV-induced natural killer cytotoxicity was dependent on MyD88 and STING. Thus, MyD88 and STING contribute to MCMV control in distinct cell types that initiate downstream immune responses.

Original language	English (US)
Article number	e56882
Pages (from-to)	1-21
Number of pages	21
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/eLife.56882
State	Published - Jul 2020

ASJC Scopus subject areas

Neuroscience(all)
Immunology and Microbiology(all)
Biochemistry, Genetics and Molecular Biology(all)

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10.7554/eLife.56882

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@article{e9351494d01840dea564c67468b26d78,

title = "Virus infection is controlled by hematopoietic and stromal cell sensing of murine cytomegalovirus through sting",

abstract = "Recognition of DNA viruses, such as cytomegaloviruses (CMVs), through pattern-recognition receptor (PRR) pathways involving MyD88 or STING constitute a first-line defense against infections mainly through production of type I interferon (IFN-I). However, the role of these pathways in different tissues is incompletely understood, an issue particularly relevant to the CMVs which have broad tissue tropisms. Herein, we contrasted anti-viral effects of MyD88 versus STING in distinct cell types that are infected with murine CMV (MCMV). Bone marrow chimeras revealed STING-mediated MCMV control in hematological cells, similar to MyD88. However, unlike MyD88, STING also contributed to viral control in non-hematological, stromal cells. Infected splenic stromal cells produced IFN-I in a cGAS-STING-dependent and MyD88-independent manner, while we confirmed plasmacytoid dendritic cell IFN-I had inverse requirements. MCMV-induced natural killer cytotoxicity was dependent on MyD88 and STING. Thus, MyD88 and STING contribute to MCMV control in distinct cell types that initiate downstream immune responses.",

author = "Piersma, {Sytse J.} and Jennifer Poursine-Laurent and Liping Yang and Barber, {Glen N.} and Parikh, {Bijal A.} and Yokoyama, {Wayne M.}",

note = "Funding Information: This work was supported by NIH grant R01-AI131680 to WMY and SJP was supported by the Netherlands Organisation for Scientific Research (Rubicon grant 825.11.004). Funding Information: We thank Beatrice Plougastel-Douglas for critically reading the manuscript. This work was supported by NIH grant R01-AI131680 to WMY and SJP was supported by the Netherlands Organisation for Scientific Research (Rubicon grant 825.11.004). National Institute of Allergy and Infectious Diseases R01-AI131680 Wayne M Yokoyama Nederlandse Organisatie voor Wetenschappelijk Onderzoek Rubicon grant 825.11.004 Sytse J Piersma. Publisher Copyright: {\textcopyright} Piersma et al.",

year = "2020",

month = jul,

doi = "10.7554/eLife.56882",

language = "English (US)",

volume = "9",

pages = "1--21",

journal = "eLife",

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T1 - Virus infection is controlled by hematopoietic and stromal cell sensing of murine cytomegalovirus through sting

AU - Piersma, Sytse J.

AU - Poursine-Laurent, Jennifer

AU - Yang, Liping

AU - Barber, Glen N.

AU - Parikh, Bijal A.

AU - Yokoyama, Wayne M.

N1 - Funding Information: This work was supported by NIH grant R01-AI131680 to WMY and SJP was supported by the Netherlands Organisation for Scientific Research (Rubicon grant 825.11.004). Funding Information: We thank Beatrice Plougastel-Douglas for critically reading the manuscript. This work was supported by NIH grant R01-AI131680 to WMY and SJP was supported by the Netherlands Organisation for Scientific Research (Rubicon grant 825.11.004). National Institute of Allergy and Infectious Diseases R01-AI131680 Wayne M Yokoyama Nederlandse Organisatie voor Wetenschappelijk Onderzoek Rubicon grant 825.11.004 Sytse J Piersma. Publisher Copyright: © Piersma et al.

PY - 2020/7

Y1 - 2020/7

N2 - Recognition of DNA viruses, such as cytomegaloviruses (CMVs), through pattern-recognition receptor (PRR) pathways involving MyD88 or STING constitute a first-line defense against infections mainly through production of type I interferon (IFN-I). However, the role of these pathways in different tissues is incompletely understood, an issue particularly relevant to the CMVs which have broad tissue tropisms. Herein, we contrasted anti-viral effects of MyD88 versus STING in distinct cell types that are infected with murine CMV (MCMV). Bone marrow chimeras revealed STING-mediated MCMV control in hematological cells, similar to MyD88. However, unlike MyD88, STING also contributed to viral control in non-hematological, stromal cells. Infected splenic stromal cells produced IFN-I in a cGAS-STING-dependent and MyD88-independent manner, while we confirmed plasmacytoid dendritic cell IFN-I had inverse requirements. MCMV-induced natural killer cytotoxicity was dependent on MyD88 and STING. Thus, MyD88 and STING contribute to MCMV control in distinct cell types that initiate downstream immune responses.

AB - Recognition of DNA viruses, such as cytomegaloviruses (CMVs), through pattern-recognition receptor (PRR) pathways involving MyD88 or STING constitute a first-line defense against infections mainly through production of type I interferon (IFN-I). However, the role of these pathways in different tissues is incompletely understood, an issue particularly relevant to the CMVs which have broad tissue tropisms. Herein, we contrasted anti-viral effects of MyD88 versus STING in distinct cell types that are infected with murine CMV (MCMV). Bone marrow chimeras revealed STING-mediated MCMV control in hematological cells, similar to MyD88. However, unlike MyD88, STING also contributed to viral control in non-hematological, stromal cells. Infected splenic stromal cells produced IFN-I in a cGAS-STING-dependent and MyD88-independent manner, while we confirmed plasmacytoid dendritic cell IFN-I had inverse requirements. MCMV-induced natural killer cytotoxicity was dependent on MyD88 and STING. Thus, MyD88 and STING contribute to MCMV control in distinct cell types that initiate downstream immune responses.

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SN - 2050-084X

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ER -

Virus infection is controlled by hematopoietic and stromal cell sensing of murine cytomegalovirus through sting

Abstract

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