Interferon Partly Dictates a Divergent Transcriptional Response in Poxvirus-Infected and Bystander Inflammatory Monocytes
Inflammatory monocytes (iMOs) and B cells are the main targets of the poxvirus ectromelia virus (ECTV) in the lymph nodes of mice and play distinct roles in surviving the infection. Infected and bystander iMOs control ECTV's systemic spread, preventing early death, while B cells make antibodies that eliminate ECTV. Our work demonstrates that within an infected animal that survives ECTV infection, intrinsic and bystander infection of iMOs and B cells differentially control the transcription of genes important for immune cell function and, perhaps, cell identity. Bystander cells upregulate metabolism, antigen presentation, and interferon-stimulated genes. Infected cells downregulate many cell-type-specific genes and upregulate transcripts typical of non-immune cells. Bystander (Bys) and infected (Inf) iMOs non-redundantly contribute to the cytokine milieu and the interferon response. Furthermore, we uncover how type I interferon (IFN-I) or IFN-γ signaling differentially regulates immune pathways in Inf and Bys iMOs and that, at steady state, IFN-I primes iMOs for rapid IFN-I production and antigen presentation.
Melo-Silva, Carolina R; Roman, Marisa I; Knudson, Cory J; Tang, Lingjuan; Xu, Ren-Huan; Tassetto, Michel; Dolan, Patrick; Andino, Raul; and Sigal, Luis J., "Interferon Partly Dictates a Divergent Transcriptional Response in Poxvirus-Infected and Bystander Inflammatory Monocytes" (2022). Department of Microbiology and Immunology Faculty Papers. Paper 167.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
This article is the author’s final published version in Cell Reports, Volume 41, Issue 8, November 2022, Article number 111676.
The published version is available at https://doi.org/10.1016/j.celrep.2022.111676. Copyright © Melo-Silva et al.