title: Controls for lung dendritic cell maturation and migration during respiratory viral infection.
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-alpha 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.
authors.affiliation: Division of Allergy and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. wheeze@allergist.com
authors.forename: Mitchell H
authors.initials: MH
authors.lastname: Grayson
authors.forename: Madeleine S
authors.initials: MS
authors.lastname: Ramos
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Rohlfing
authors.forename: Robert
authors.initials: R
authors.lastname: Kitchens
authors.forename: Howard D
authors.initials: HD
authors.lastname: Wang
authors.forename: Aaron
authors.initials: A
authors.lastname: Gould
authors.forename: Eugene
authors.initials: E
authors.lastname: Agapov
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Holtzman
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D007165:Immunosuppression Therapy; D008168:Lung / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011024:Pneumonia, Viral / Q000276:immunology* / Q000473:pathology / Q000821:virology; D019713:Receptors, CCR5 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D010253:Respirovirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D029082:Sendai virus / Q000276:immunology
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019713:Receptors, CCR5