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The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens

Yen-Michael S Hsu1, Yongliang Zhang, Yun You

  • 1Department of Molecular and Cellular Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

Nature Immunology
|December 26, 2006
PubMed

Insights

Caspase-recruitment domain-containing adaptor protein CARD9 is essential for innate immunity against intracellular pathogens. CARD9 deficiency impairs macrophage activation and host defense, highlighting its critical role in immune signaling pathways.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • The caspase-recruitment domain-containing adaptor protein CARD9 (CARD9) is known to regulate innate immune responses to fungal infections.
  • Its role in defense against intracellular bacterial and viral pathogens remains less understood.

Purpose of the Study:

  • To investigate the function of CARD9 in innate immune responses against intracellular pathogens.
  • To elucidate the molecular mechanisms underlying CARD9's role in immune signaling.

Main Methods:

  • Generation and analysis of Card9 knockout (Card9(-/-)) mice.
  • Assessment of macrophage activation, kinase activity (p38, Jnk, NF-kappaB), and cytokine production.
  • Investigation of CARD9 interactions with Nod2 and RICK in response to infection.

Main Results:

  • Card9(-/-) macrophages exhibited impaired activation of p38 and Jnk kinases, but not NF-kappaB, following bacterial and viral challenge.
  • Card9(-/-) mice showed compromised clearance of Listeria monocytogenes infection and altered cytokine profiles.
  • CARD9 was found to inducibly associate with Nod2 and RICK in wild-type cells.

Conclusions:

  • CARD9 is crucial for innate immune responses against intracellular pathogens, extending beyond its known role in fungal immunity.
  • CARD9 mediates Nod2-dependent activation of p38 and Jnk signaling pathways, which are critical for effective host defense.
  • These findings identify CARD9 as a key regulator in the innate immune system's response to a broader range of microbial threats.

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