The host immune response in respiratory virus infection: balancing virus clearance and immunopathology

Semin Immunopathol. 2016 Jul;38(4):471-82. doi: 10.1007/s00281-016-0558-0. Epub 2016 Mar 10.


The respiratory tract is constantly exposed to the external environment, and therefore, must be equipped to respond to and eliminate pathogens. Viral clearance and resolution of infection requires a complex, multi-faceted response initiated by resident respiratory tract cells and innate immune cells and ultimately resolved by adaptive immune cells. Although an effective immune response to eliminate viral pathogens is essential, a prolonged or exaggerated response can damage the respiratory tract. Immune-mediated pulmonary damage is manifested clinically in a variety of ways depending on location and extent of injury. Thus, the antiviral immune response represents a balancing act between the elimination of virus and immune-mediated pulmonary injury. In this review, we highlight major components of the host response to acute viral infection and their role in contributing to mitigating respiratory damage. We also briefly describe common clinical manifestations of respiratory viral infection and morphological correlates. The continuing threat posed by pandemic influenza as well as the emergence of novel respiratory viruses also capable of producing severe acute lung injury such as SARS-CoV, MERS-CoV, and enterovirus D68, highlights the need for an understanding of the immune mechanisms that contribute to virus elimination and immune-mediated injury.

Keywords: Inflammatory response; Influenza; Lungs; Respiratory infection; Virus.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity
  • Animals
  • Cytokines / metabolism
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immunity*
  • Immunity, Innate
  • Inflammation Mediators / metabolism
  • Interferons / metabolism
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / metabolism
  • Pathogen-Associated Molecular Pattern Molecules / metabolism
  • Receptors, Pattern Recognition / metabolism
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / virology
  • Respiratory Tract Infections / immunology*
  • Respiratory Tract Infections / metabolism
  • Respiratory Tract Infections / pathology
  • Respiratory Tract Infections / virology*


  • Cytokines
  • Inflammation Mediators
  • Pathogen-Associated Molecular Pattern Molecules
  • Receptors, Pattern Recognition
  • Interferons