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 infec-tion 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 cyto-kine milieu and the interferon response. Furthermore, we uncover how type I interferon (IFN-I) or IFN-g 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.

Automated summary

The study reveals that infected and bystander inflammatory monocytes (iMOs) and B cells differentially control gene transcription important for immune cell function and cell identity. Bystander cells upregulate metabolism and interferon-stimulated genes, while infected cells downregulate cell-type-specific genes and upregulate genes typical of non-immune cells.