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A role for NKG2D in NK cell-mediated resistance to poxvirus disease

Min Fang1, Lewis L Lanier, Luis J Sigal

  • 1Program of Viral Pathogenesis, Division of Basic Sciences, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.

Plos Pathogens
|February 13, 2008
PubMed

Insights

Natural killer (NK) cells are crucial for C57BL/6 mice resistance to Ectromelia virus (ECTV) infection. Their direct killing ability and support for T cell responses, particularly via NKG2D, are key to fighting mousepox.

Area of Science:

  • Immunology
  • Virology
  • Genetics

Background:

  • Ectromelia virus (ECTV) causes mousepox, a disease analogous to human smallpox.
  • C57BL/6 (B6) mice exhibit natural resistance to ECTV, attributed to innate and adaptive immunity.
  • Natural killer (NK) cells are known innate immune components vital for B6 mice resistance, but their precise mechanism against orthopoxviruses (OPVs) is unclear.

Purpose of the Study:

  • To elucidate the mechanism of NK cell-mediated resistance to ECTV infection in B6 mice.
  • To determine the role of NK cell cytolytic function and T cell response modulation in mousepox resistance.
  • To investigate the involvement of the activating receptor NKG2D in NK cell-mediated antiviral immunity.

Main Methods:

  • Comparative analysis of ECTV-infected B6 mice with varying NK cell functionalities.
  • Assessment of NK cell direct cytotoxicity against infected cells.
  • Evaluation of NK cell impact on T cell responses post-infection.
  • Examination of disease progression and lethality in the presence or absence of NKG2D signaling.

Main Results:

  • B6 mice resistance to mousepox depends on NK cells' direct cytolytic activity.
  • NK cells enhance T cell responses, contributing to viral clearance.
  • The activating receptor NKG2D is essential for effective NK cell-mediated protection against ECTV.
  • NKG2D is critical for controlling disease severity and preventing lethality.

Conclusions:

  • NK cells employ direct cytotoxicity and T cell boosting to confer resistance against ECTV.
  • NKG2D-mediated signaling is indispensable for optimal NK cell function in combating mousepox.
  • Understanding these mechanisms provides insights into natural resistance against viral pathogens.

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