CARD9 facilitates microbe-elicited production of reactive oxygen species by regulating the LyGDI-Rac1 complex (Nat Immunol, 2009, 10:1208-1214)

報告日期: 2010/03/23
報告時間: 17:10/18:00
報告學生: 蔡宗婷
講評老師: 謝奇璋
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990323-3.pdf

CARD9 facilitates microbe-elicited production of reactive oxygen species by regulating the LyGDI-Rac1 complex

 

Wu W., et al. Nat Immunol. 10:1208 -1214 (2009).

 

Speaker: 蔡宗婷

Commentator: 謝奇璋老師

Time:2010/3/23  17:10-18:00

Place:Room 602

 

Abstract

The innate immune system is a first line of host defense mechanism during infection. On bacterial infection, macrophages phgocytosis the bacteria and generate the reactive oxygen species (ROS) to kill the bacteria. How phagocytosis induces ROS production is not clear. CARD9 is a caspase recruitment domain containing adaptor protein, consist of coiled coil in the c-terminal domain, and mostly expressed in myeloid cells. It is required for tyrosine kinase and Toll-like receptor–induced activation of dendritic cells to trigger the activation of mitogen-activated protein kinases and NF-κB. In addition, CARD9-deficient mice are susceptible to Listeria monocytogenes and fungal infection. The production of proinfammatory cytokines are also impaired. lyGDI, a GDP-dissociation inhibitory protein plays the essential role in ROS production during the NADPH oxidase activation. In this study, the auther use the retrovirus-based protein-fragment complementation assay screening system to identify a CARD9-asscoiated lyGDI after challenge with heat inactivated L. monocytogenes. The CARD9 and lyGDI was found to colocalize in bacteria-containing phagoaomes. On CARD9-Cherry protein expressed RAW264.7 cells, LyGDI binds to CARD9-Cherry after L. monocytogenes stimulation. CARD9 inhibited the interaction between LyGDI and Rac1, then led to Rac1 activation, which promotes the production of ROS and bacteria clearing in macrophages. This study identifies CARD9 is a key adaptor protein in participating on microbe-elicited ROS production by regulating the lyGDI-Rac1 complex.

 

References

1.  Hara H and Saito T. CARD9 versus CARMA1 in innate and adaptive immunity. Trends Immunol.30:234-42 (2009).

2.  Hsu YM, et al. The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Nat Immunol.8:198-205 (2007).

3.  Hara H, et al. The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors. Nat Immunol. 8:619-29 (2007).