Redundant function of plasmacytoid and conventional dendritic cells is required to survive a natural virus infection

Lauren W. Kaminsky, Janet J. Sei, Nikhil J. Parekh, Michael L. Davies, Irene E. Reider, Tracy E. Krouse, Christopher C. Norbury

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Viruses that spread systemically from a peripheral site of infection cause morbidity and mortality in the human population. Innate myeloid cells, including monocytes, macrophages, monocyte-derived dendritic cells (mo-DC), and dendritic cells (DC), respond early during viral infection to control viral replication, reducing virus spread from the peripheral site. Ectromelia virus (ECTV), an orthopoxvirus that naturally infects the mouse, spreads systemically from the peripheral site of infection and results in death of susceptible mice. While phagocytic cells have a requisite role in the response to ECTV, the requirement for individual myeloid cell populations during acute immune responses to peripheral viral infection is unclear. In this study, a variety of myeloid- specific depletion methods were used to dissect the roles of individual myeloid cell subsets in the survival of ECTV infection. We showed that DC are the primary producers of type I interferons (T1-IFN), requisite cytokines for survival, following ECTV infection. DC, but not macrophages, monocytes, or granulocytes, were required for control of the virus and survival of mice following ECTV infection. Depletion of either plasmacytoid DC (pDC) alone or the lymphoid-resident DC subset (CD8α+ DC) alone did not confer lethal susceptibility to ECTV. However, the function of at least one of the pDC or CD8α+ DC subsets is required for survival of ECTV infection, as mice depleted of both populations were susceptible to ECTV challenge. The presence of at least one of these DC subsets is sufficient for cytokine production that reduces ECTV replication and virus spread, facilitating survival following infection.

Original languageEnglish (US)
Pages (from-to)9974-9985
Number of pages12
JournalJournal of virology
Volume89
Issue number19
DOIs
StatePublished - Jan 1 2015

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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