Neutrophils Sustain Effective CD8(+) T-cell Responses in the Respiratory Tract Following Influenza Infection

Immunol Cell Biol. 2012 Feb;90(2):197-205. doi: 10.1038/icb.2011.26. Epub 2011 Apr 12.

Abstract

Neutrophils have an important role in early host protection during influenza A virus infection. Their ability to modulate the virus-specific adaptive immune response is less clear. Here, we have used a mouse model to examine the impact of neutrophils on CD8(+) T-cell responses during influenza virus infection. CD8(+) T-cell priming, expansion, migration, cytokine secretion and cytotoxic capacity were investigated in the virus-infected airways and secondary lymphoid organs. To do this, we utilised a Ly6G-specific monoclonal antibody (mAb; 1A8) that specifically depletes neutrophils in vivo. Neutrophil depletion early after infection with influenza virus strain HKx31 (H3N2) did not alter influenza virus-derived antigen presentation or naïve CD8(+) T-cell expansion in the secondary lymphoid organs. Trafficking of virus-specific CD8(+) T cells into the infected pulmonary airways was also unaltered. Instead, early neutropenia reduced both the overall magnitude of influenza virus-specific CD8(+) T cells, together with impaired cytokine production and cytotoxic effector function. Therefore, neutrophils are important participants in anti-viral mechanisms that sustain effective CD8(+) T-cell responses in the respiratory tract of influenza virus-infected mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Movement / immunology
  • Cell Proliferation
  • Granzymes / analysis
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / pathogenicity
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / prevention & control
  • Orthomyxoviridae Infections / virology
  • Respiratory System / immunology*
  • Respiratory System / pathology
  • Respiratory System / virology

Substances

  • Antibodies, Monoclonal
  • Granzymes