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Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1

Roi Gazit1, Raizy Gruda, Moran Elboim

  • 1The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.

Nature Immunology
|March 28, 2006
PubMed

Insights

Natural killer cells eliminate viruses and tumors using specific receptors. This study shows the natural cytotoxicity receptor 1 (NCR1) is critical for clearing influenza virus in vivo.

Area of Science:

  • Immunology
  • Virology
  • Cancer Research

Background:

  • Natural killer (NK) cells are crucial for innate immunity, eliminating viruses and tumors.
  • NK cell activity is regulated by activating and inhibitory receptors, including NKp46 (NCR1 in mice).
  • The in vivo role of NCR1 in host defense remains incompletely understood.

Purpose of the Study:

  • To investigate the in vivo function of the principal activating NK cell receptor, NCR1.
  • To assess the impact of NCR1 deficiency on tumor spread and viral infection.
  • To track NK cell accumulation at infection sites using a reporter system.

Main Methods:

  • Generated Ncr1(gfp/gfp) mice by replacing the Ncr1 gene with a green fluorescent protein (GFP) reporter cassette.
  • Challenged mice with specific tumors and influenza virus.
  • Monitored tumor growth and survival.
  • Tracked NK cell localization by detecting GFP fluorescence at infection sites.

Main Results:

  • Ncr1(gfp/gfp) mice exhibited enhanced tumor spread in the 129/Sv strain but not C57BL/6.
  • Influenza virus infection was lethal in both 129/Sv and C57BL/6 Ncr1(gfp/gfp) mice.
  • GFP tracking revealed accumulation of NK cells at influenza infection sites.

Conclusions:

  • NCR1 plays a critical role in the in vivo eradication of influenza virus.
  • Ncr1 deficiency impairs host defense against influenza, leading to increased mortality.
  • The study highlights the importance of NCR1 in antiviral immunity.

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