The innate immune rheostat: influence on lung inflammatory disease and secondary bacterial pneumonia.
The activity of innate immunity is not simply dictated by the presence of an antigen but also by the balance between negative regulatory and immune potentiator pathways. Even in the absence of antigen, innate immunity can 'inflame' if negative regulators are absent. This resting state is adaptable and dictated by environmental influences, host genetics and past infection history. A return to homoeostasis post inflammation may therefore not leave the tissue in an identical state to that prior to the inflammatory event. This adaptability makes us all unique and also explains the variable outcome experienced by a diverse population to the same inflammatory stimulus. Using murine models we have identified that influenza virus causes a long-term modification of the lung microenvironment by a de-sensitization to bacterial products and an increase in the myeloid negative regulator CD200R (CD200 receptor). These two events prevent subsequent inflammatory damage while the lung is healing, but also they may predispose to bacterial colonization of the lower respiratory tract should regulatory mechanisms overshoot. In the extreme, this leads to bacterial pneumonia, sepsis and death. A deeper understanding of the consequences arising from innate immune cell alteration during influenza infection and the subsequent development of bacterial complications has important implications for future drug development.
Hussell
Tracy
T
Imperial College London, Leukocyte Biology Section, National Heart and Lung Institute, London SW7 2AZ, UK. t.hussell@imperial.ac.uk
Cavanagh
Mary M
MM
D000818:Animals; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology* / Q000502:physiology; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D008171:Lung Diseases / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism
D011956:Receptors, Cell Surface