Mar 25, 2020

Virus infection is controlled by cell type-specific sensing of murine cytomegalovirus through MyD88 and STING

BioRxiv : the Preprint Server for Biology
Max V StallerAngela DePace

Abstract

Recognition of DNA viruses, such as cytomegaloviruses (CMVs), through patternrecognition 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 investigated anti-viral effects of MyD88 and 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 plasmacytoid dendritic cell IFN-I had inverse requirements. MCMV-induced natural killer (NK) 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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