Innate immunity plays a crucial role in initiating the immune responses and pathogen clearance upon microbial infection. Using pattern recognition receptors including cell surface receptor such as Toll-like receptors (TLRs) or intracellular receptors such as NOD-like receptors (NLRs), host cells sense and respond to microbial infection, which triggers the activation of various signaling events, leading to anti-microbial and inflammatory responses. Understanding the signaling pathways induced by various microbial infections will provide the molecular insights into the host defense machinery and provide the potential therapeutic targets for anti-microbial infection. Recent studies from our lab and others indicate that CARD9, a Caspase Recruitment Domain (CARD)-containing adaptor protein, plays an important role in innate immune responses through regulation of NF-kB and MAP kinases. Interestingly, we have found that CARD9 physically associates with bacteria-containing phagosomes and is directly involved in the clearance of infected bacteria in macrophages. However, the molecular mechanism by which CARD9 is involved in the regulation of these responses remains to be determined. To further study the biological function of CARD9, we propose two specific aims to investigate the molecular mechanism by which CARD9 mediates antimicrobial responses using our recently generated CARD9-deficient (Card9-/-) mice.
Our specific aims are: (1) to determine the molecular mechanism by which CARD9 is involved in the clearance of intracellular bacteria;(2) to identify CARD9-interacting proteins that mediate CARD9-dependent anti-bacterial and fungal responses. Together, these studies will reveal an unknown host defense mechanism and provide the novel insight into anti-microbial immune responses.

Public Health Relevance

Innate immunity plays a crucial role in initiating the immune responses and pathogen clearance upon microbial infection. In this proposal, we will determine the molecular mechanism by which CARD9, a scaffold molecule, is involved in regulation of innate immune responses against microbial infection. Results from these studies will provide molecular insights for new therapeutic approaches against microbial infection.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Innate Immunity and Inflammation Study Section (III)
Program Officer
Palker, Thomas J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas MD Anderson Cancer Center
Other Domestic Higher Education
United States
Zip Code
Jiang, Changying; Zhou, Zhicheng; Quan, Yanping et al. (2016) CARMA3 Is a Host Factor Regulating the Balance of Inflammatory and Antiviral Responses against Viral Infection. Cell Rep 14:2389-401
Blonska, Marzenna; Zhu, Yifan; Chuang, Hubert H et al. (2015) Jun-regulated genes promote interaction of diffuse large B-cell lymphoma with the microenvironment. Blood 125:981-91
Zhao, Xue-Qiang; Zhu, Le-Le; Chang, Qing et al. (2014) C-type lectin receptor dectin-3 mediates trehalose 6,6'-dimycolate (TDM)-induced Mincle expression through CARD9/Bcl10/MALT1-dependent nuclear factor (NF)-?B activation. J Biol Chem 289:30052-62
Wang, Huafeng; LeBert, Vanessa; Hung, Chiung Yu et al. (2014) C-type lectin receptors differentially induce th17 cells and vaccine immunity to the endemic mycosis of North America. J Immunol 192:1107-1119
Yang, M; Shao, J-H; Miao, Y-J et al. (2014) Tumor cell-activated CARD9 signaling contributes to metastasis-associated macrophage polarization. Cell Death Differ 21:1290-302
Jia, Xin-Ming; Tang, Bing; Zhu, Le-Le et al. (2014) CARD9 mediates Dectin-1-induced ERK activation by linking Ras-GRF1 to H-Ras for antifungal immunity. J Exp Med 211:2307-21
Cheng, Qianqian; Zhang, Qingfeng; Xu, Xindong et al. (2014) MAPK phosphotase 5 deficiency contributes to protection against blood-stage Plasmodium yoelii 17XL infection in mice. J Immunol 192:3686-96
Zhong, Bo; Liu, Xikui; Wang, Xiaohu et al. (2013) Ubiquitin-specific protease 25 regulates TLR4-dependent innate immune responses through deubiquitination of the adaptor protein TRAF3. Sci Signal 6:ra35
Liu, Xikui; Li, Hongxiu; Zhong, Bo et al. (2013) USP18 inhibits NF-?B and NFAT activation during Th17 differentiation by deubiquitinating the TAK1-TAB1 complex. J Exp Med 210:1575-90
Zhu, Le-Le; Zhao, Xue-Qiang; Jiang, Changying et al. (2013) C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection. Immunity 39:324-34

Showing the most recent 10 out of 32 publications