title: Lowering the threshold of lung innate immune cell activation alters susceptibility to secondary bacterial superinfection.
abstract: BACKGROUND
  Previous studies have shown that the interaction of CD200R, a myeloid inhibitory receptor, with its ligand, CD200, is critical in the control of innate immune activation in the lung.
  
  
  RESULTS
  Using a mouse model of bacterial superinfection following influenza, we show that an absence of CD200R (a negative regulator highly expressed by macrophages and dendritic cells), restricts commensal and exogenous bacterial invasiveness and completely prevents the mortality observed in wild-type mice. This benefit is due to a heightened innate immune response to influenza virus in cd200r knockout mice that limits immune pathogenesis and viral load. In wild-type mice, apoptotic cells expressing CD200 that we believe contribute to the suppressed innate immune response to bacteria dominate during the resolution phase of influenza-induced inflammation. We also show for the first time the presence of a variety of previously unidentified bacterial species in the lower airways that are significantly adjusted by influenza virus infection and may contribute to the pathophysiology of disease.
  
  
  CONCLUSIONS
  The interaction of CD200 with CD200R therefore contributes to the hyporesponsive innate immune state following influenza virus infection that predisposes to secondary bacterial infection, a phenomenon that has the potential for immune modulation.
authors: Leukocyte Biology Section, Imperial College London, National Heart and Lung Institute, United Kingdom.
authors: John
authors: J
authors: Goulding
authors: Alexandra
authors: A
authors: Godlee
authors: Seema
authors: S
authors: Vekaria
authors: Markus
authors: M
authors: Hilty
authors: Robert
authors: R
authors: Snelgrove
authors: Tracy
authors: T
authors: Hussell
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D005260:Female; D007113:Immunity, Innate; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015163:Superinfection / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C492346:CD200 receptor, mouse; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; C042739:antigens, CD200