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

Nature Immunology, 8, 198-205 (2007)

Speaker: 顏嘉良                                                            Place: Room 601

Commentator: 楊倍昌老師                                           Date: 2006/3/21 15:00-16:00

Abstract:

The innate immune system provides a rapid response to pathogens, which relies on the detection of pathogen-associated molecular patterns (PAMPs) by the pattern-recognition molecules (PRMs).  The first intracellular PAMPs sensors discovered are NOD1 and 2, which detect bacterial peptidoglycan (PGN) or their hydrolyzed byproduct muramyl dipeptide (MDP).  These receptors use a CARD (caspase-recruitment domain)-dependent mechanism to recruit serine-threonine kinase RICK (also called RIP2) and activate MAPKs and NF-κB.  However, the signaling pathways involved in NOD-induced innate immune activation are still unknown.  In this study, the authors focused on CARD9, an adaptor protein which was thought to be a key adaptor in innate immune signaling to activate NF- κB after fungal infection.  Other findings showed that CARD9 strongly activates the kinases p38 and Jnk.  The authors used CARD9^-/- mice to determine the involvement of CARD9 in innate immune responses.  First, they found that CARD9 was expressed mainly in innate immune cells, and macrophages from CARD9^-/- mice failed to respond to different NOD2 or TLR agonists, suggesting that CARD9 is involved in a variety of innate immune responses.  Secondly, they found that macrophages from CARD9^-/- mice failed to activate p38.  Overexpression of CARD9 or NOD2 alone can activate p38 slightly, overexpression of CARD9 and NOD2 together acts synergy in the activation of p38, but not of NF-κB, suggesting that CARD9 may be a signaling component downstream of NOD2, leading to activation of MAPK.  The authors finally found that CARD9^-/- mice failed to mount antibacterial immunity.   These findings revealed that adaptor protein CARD9 is essential for the intracellular innate immune responses, and these immune responses controlled by CARD9 are distinct from TLR- and NF-κB- signals.

References:

1.          Gross, O. et al. CARD9 controls a non-TLR signaling pathway for innate anti-fungal immunity. Nature, 442, 651-656 (2006).

2.          Etienne Meylan, et al. Intracellular pattern recognition receptors in the host response. Nature, 442, 39-44 (2006).