Controls for lung dendritic cell maturation and migration during respiratory viral infection

Mitchell H. Grayson, Madeleine S. Ramos, Michelle M. Rohlfing, Robert Kitchens, Howard D. Wang, Aaron Gould, Eugene Agapov, Michael J. Holtzman

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Dendritic cells are ideally suited to orchestrate the innate and adaptive immune responses to infection, but we know little about how these cells respond to infection with common respiratory viruses. Paramyxoviral infections are the most frequent cause of serious respiratory illness in childhood and are associated with an increased risk of asthma. We therefore used a high-fidelity mouse model of paramyxoviral respiratory infection triggered by Sendai virus to examine the response of conventional and plasmacytoid dendritic cells (cDCs and pDCs, respectively) in the lung. We found that pDCs are scarce at baseline but become the predominant population of lung dendritic cells during infection. This recruitment allows for a source of IFN-α locally at the site of infection. In contrast, cDCs rapidly differentiate into myeloid cDCs and begin to migrate from the lung to draining lymph nodes within 2 h after viral inoculation. These events cause the number of lung cDCs to decrease rapidly and remain decreased at the site of viral infection. Maturation and migration of lung cDCs depends on Ccl5 and Ccr5 signals because these events are significantly impaired in Ccl5-/- and Ccr5-/- mice. cDCs failure to migrate to draining lymph nodes in Ccl5-/- or Ccr5 -/- mice is associated with impaired up-regulation of CCR7 that would normally direct this process. Our results indicate that pDCs and cDCs respond distinctly to respiratory paramyxoviral infection with patterns of movement that should serve to coordinate the innate and adaptive immune responses, respectively.

Original languageEnglish
Pages (from-to)1438-1448
Number of pages11
JournalJournal of Immunology
Volume179
Issue number3
DOIs
StatePublished - Aug 1 2007

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    Grayson, M. H., Ramos, M. S., Rohlfing, M. M., Kitchens, R., Wang, H. D., Gould, A., Agapov, E., & Holtzman, M. J. (2007). Controls for lung dendritic cell maturation and migration during respiratory viral infection. Journal of Immunology, 179(3), 1438-1448. https://doi.org/10.4049/jimmunol.179.3.1438