TY - JOUR
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 - 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.
UR - http://www.scopus.com/inward/record.url?scp=85089302008&partnerID=8YFLogxK
U2 - 10.7554/eLife.56882
DO - 10.7554/eLife.56882
M3 - Article
C2 - 32723479
AN - SCOPUS:85089302008
SN - 2050-084X
VL - 9
SP - 1
EP - 21
JO - eLife
JF - eLife
M1 - e56882
ER -