Persistent and compartmentalised disruption of dendritic cell subpopulations in the lung following influenza A virus infection.
Immunological homeostasis in the respiratory tract is thought to require balanced interactions between networks of dendritic cell (DC) subsets in lung microenvironments in order to regulate tolerance or immunity to inhaled antigens and pathogens. Influenza A virus (IAV) poses a serious threat of long-term disruption to this balance through its potent pro-inflammatory activities. In this study, we have used a BALB/c mouse model of A/PR8/34 H1N1 Influenza Type A Virus infection to examine the effects of IAV on respiratory tissue DC subsets during the recovery phase following clearance of the virus. In adult mice, we found differences in the kinetics and activation states of DC residing in the airway mucosa (AMDC) compared to those in the parenchymal lung (PLDC) compartments. A significant depletion in the percentage of AMDC was observed at day 4 post-infection that was associated with a change in steady-state CD11b+ and CD11b- AMDC subset frequencies and significantly elevated CD40 and CD80 expression and that returned to baseline by day 14 post-infection. In contrast, percentages and total numbers of PLDC were significantly elevated at day 14 and remained so until day 21 post-infection. Accompanying this was a change in CD11b+and CD11b- PLDC subset frequencies and significant increase in CD40 and CD80 expression at these time points. Furthermore, mice infected with IAV at 4 weeks of age showed a significant increase in total numbers of PLDC, and increased CD40 expression on both AMDC and PLDC, when analysed as adults 35 days later. These data suggest that the rate of recovery of DC populations following IAV infection differs in the mucosal and parenchymal compartments of the lung and that DC populations can remain disrupted and activated for a prolonged period following viral clearance, into adulthood if infection occurred early in life.
Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, W.A., Australia.
Deborah H
DH
Strickland
Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, W.A., Australia.
Vanessa
V
Fear
Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, W.A., Australia; School of Veterinary and Life Sciences, Murdoch University, Perth, W.A., Australia.
Seth
S
Shenton
Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, W.A., Australia.
Mathew E
ME
Wikstrom
Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, W.A., Australia; School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
Graeme
G
Zosky
Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, W.A., Australia.
Alexander N
AN
Larcombe
Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, W.A., Australia; Queensland Children's Medical Research Institute, University of Queensland, Brisbane, Qld., Australia.
Patrick G
PG
Holt
School of Veterinary and Life Sciences, Murdoch University, Perth, W.A., Australia.
Cassandra
C
Berry
Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, W.A., Australia; Pulmonary Medicine, Bern University Hospital and Department of Clinical Research, Berne University, Berne, Switzerland.
Christophe
C
von Garnier
Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, W.A., Australia; School of Veterinary and Life Sciences, Murdoch University, Perth, W.A., Australia.
Philip A
PA
Stumbles
D000375:Aging / Q000473:pathology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D039481:CD11b Antigen / Q000378:metabolism; D002451:Cell Compartmentation; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D009980:Influenza A virus / Q000276:immunology*; D007700:Kinetics; D008168:Lung / Q000276:immunology* / Q000821:virology*; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D013997:Time Factors
D015703:Antigens, CD; D015415:Biomarkers; D039481:CD11b Antigen; D016207:Cytokines