Brucella TIR-like protein TcpB/Btp1 specifically targets the host adaptor protein MAL/TIRAP to promote infection.
Brucella spp. are known to avoid host immune recognition and weaken the immune response to infection. Brucella like accomplish this by employing two clever strategies, called the stealth strategy and hijacking strategy. The TIR domain-containing protein (TcpB/Btp1) of Brucella melitensis is thought to be involved in inhibiting host NF-κB activation by binding to adaptors downstream of Toll-like receptors. However, of the five TIR domain-containing adaptors conserved in mammals, whether MyD88 or MAL, even other three adaptors, are specifically targeted by TcpB has not been identified. Here, we confirmed the effect of TcpB on B.melitensis virulence in mice and found that TcpB selectively targets MAL. By using siRNA against MAL, we found that TcpB from B.melitensis is involved in intracellular survival and that MAL affects intracellular replication of B.melitensis. Our results confirm that TcpB specifically targets MAL/TIRAP to disrupt downstream signaling pathways and promote intra-host survival of Brucella spp.
School of Public Health, Jilin University, Changchun, 130021, People's Republic of China; Test Methoddology Teaching and Research Secretion, Xi'an Hygienic School, No.398 Youyi East Road, Beilin District, Xi'an, Shaanxi, 710054, People's Republic of China.
Wenna
W
Li
Institute of Disease Control and Prevention, Beijing, 100071, People's Republic of China. Electronic address: yuehuakebj@163.com.
Yuehua
Y
Ke
General Hospital of People's Armed Police Forces, Beijing, 100039, People's Republic of China.
Yufei
Y
Wang
Institute of Disease Control and Prevention, Beijing, 100071, People's Republic of China.
Mingjuan
M
Yang
Institute of Disease Control and Prevention, Beijing, 100071, People's Republic of China.
Junguang
J
Gao
Institute of Disease Control and Prevention, Beijing, 100071, People's Republic of China.
Shaoxia
S
Zhan
Institute of Disease Control and Prevention, Beijing, 100071, People's Republic of China.
Du
D
Xinying
Institute of Disease Control and Prevention, Beijing, 100071, People's Republic of China.
Liuyu
L
Huang
Department of Orthopedics, The First Affiliated Hospital of General Hospital of People's Liberation Army, Beijing, 100048, People's Republic of China. Electronic address: lwf304@163.com.
Wenfeng
W
Li
Institute of Disease Control and Prevention, Beijing, 100071, People's Republic of China; College of Medicine, Shihezi University, Shihezi, People's Republic of China; Research Center of Molecular Biology, Inner Mongolia Medical University, Hohhot, People's Republic of China. Electronic address: zeliangchen@yahoo.com.
Zeliang
Z
Chen
School of Public Health, Jilin University, Changchun, 130021, People's Republic of China. Electronic address: li_juan@jlu.edu.cn.
Juan
J
Li
D001426:Bacterial Proteins / Q000502:physiology*; D002002:Brucella / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D037521:Virulence Factors / Q000502:physiology*
D001426:Bacterial Proteins; D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; C587630:TcpB protein, Brucella melitensis; D037521:Virulence Factors
Brucella; Intracellular survival; MAL/TIRAP; NF-κB; TIR domain