The ITIM Domain-Containing NK Receptor Ly49Q Impacts Pulmonary Infection by Mediating Neutrophil Functions

J Immunol. 2018 Jun 15;200(12):4085-4093. doi: 10.4049/jimmunol.1701084. Epub 2018 Apr 30.


Pulmonary infection is a frequent pathology associated with excessive neutrophil infiltration. Ly49Q, an ITIM domain-bearing receptor expressed on different leukocytes, has been recently reported to impact neutrophil migration and polarization. Utilizing a murine model of Klebsiella pneumoniae-induced pulmonary infection in combination with additional in vivo and in vitro assays, we show that Ly49Q is critically involved in different steps of the leukocyte adhesion cascade. Ly49Q deficiency is associated with a reduced rolling velocity, impaired crawling capacity, and diminished transmigration. We show that overactivation of the neutrophil β2 integrins Mac-1 and LFA-1 is responsible for increased adhesion and reduced neutrophil transmigration, resulting in a strongly impaired immune defense against pulmonary infection. Structure function analysis in vitro and in vivo demonstrated that different domains of Ly49Q are important for its function. In summary, Ly49Q regulates integrin activation and neutrophil recruitment and is required for an adequate immune response in pulmonary infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD18 Antigens / metabolism
  • Cell Adhesion / physiology
  • Cell Movement / physiology
  • Female
  • Klebsiella Infections / metabolism
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / pathogenicity
  • Leukocytes / metabolism
  • Lung / metabolism*
  • Lung / microbiology
  • Lung Injury / metabolism*
  • Lung Injury / microbiology
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Macrophage-1 Antigen / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NK Cell Lectin-Like Receptor Subfamily A / metabolism*
  • Neutrophil Infiltration / physiology
  • Neutrophils / metabolism*
  • Neutrophils / physiology*
  • Protein Domains / physiology*


  • CD18 Antigens
  • Klra17 protein, mouse
  • Lymphocyte Function-Associated Antigen-1
  • Macrophage-1 Antigen
  • NK Cell Lectin-Like Receptor Subfamily A