AUTHOR=Lei Yingying , Cao Xiaojian , Xu Weize , Yang Bing , Xu Yangyang , Zhou Wei , Dong Shuang , Wu Qijun , Rahman Khaista , Tyagi Rohit , Zhao Shuhong , Chen Xi , Cao Gang 

TITLE=Rv3722c Promotes Mycobacterium tuberculosis Survival in Macrophages by Interacting With TRAF3

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.627798

DOI=10.3389/fcimb.2021.627798

ISSN=2235-2988

ABSTRACT=<p><italic>Mycobacterium tuberculosis</italic> (<italic>M.tb</italic>) secretes numerous proteins to interfere with host immune response for its long-term survival. As one of the top abundant <italic>M.tb</italic> secreted proteins, Rv3722c was found to be essential for bacilli growth. However, it remains elusive how this protein interferes with the host immune response and regulates <italic>M.tb</italic> survival. Here, we confirmed that Rv3722c interacted with host TRAF3 to promote <italic>M.tb</italic> replication in macrophages. Knock-down of TRAF3 attenuated the effect of Rv3722c on the intracellular <italic>M.tb</italic> survival. The interaction between Rv3722c and TRAF3 hampered MAPK and NF-κB pathways, resulting in a significant increase of IFN-β expression and decrease of IL-1β, IL-6, IL-12p40, and TNF-α expression. Our study revealed that Rv3722c interacted with TRAF3 and interrupted its downstream pathways to promote <italic>M.tb</italic> survival in macrophages. These findings facilitate further understanding of the mechanism of <italic>M.tb</italic> secreted proteins in regulating the host cell immune response and promoting its intracellular survival.</p>