DnaJ (hsp40) of Streptococcus pneumoniae is involved in bacterial virulence and elicits a strong natural immune reaction via PI3K/JNK.
As a heat shock protein, DnaJ plays an important role in the pathogenesis of pneumococcal infection. However, how the virulence factor-DnaJ elicits host natural immunity still remains unclear. In this study, we investigated the effects of dnaJ deficiency in Streptococcus pneumoniae (S. pneumoniae) on bacterial virulence, and further explored the related molecular mechanisms in vivo and in vitro. By generating dnaJ deficient mutant (ΔdnaJ), the virulence and colonization were detected in murine pneumonia and sepsis models in vivo. Compared with wild-type parent strain, the abilities of rapid colonization and induction of inflammatory responses of ΔdnaJ in mouse lungs were significantly impaired. Simultaneously, recombinant DnaJ purified from E. coli expression system (rDnaJ) induced macrophage strain RAW264.7 to secrete IL-6 by activation of PI3K and JNK signal pathways, which were confirmed by the specific signaling inhibitors. In conclusion, DnaJ, a novel virulence protein, was essential for the virulence and colonization of S. pneumoniae and induced pro-inflammatory cytokine production in macrophages through PI3K/JNK.
Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education Chongqing Medical University, 400016, Chongqing, China; The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, 400016, Chongqing, China.
Jin
J
Cui
Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education Chongqing Medical University, 400016, Chongqing, China.
Chenyu
C
Ma
Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education Chongqing Medical University, 400016, Chongqing, China; The Stomatological Hospital of Chongqing Medical University, 401147, Chongqing, China.
Guo
G
Ye
Chongqing Hospital of Traditional Chinese Medicine, 400016, Chongqing, China.
Yong
Y
Shi
Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education Chongqing Medical University, 400016, Chongqing, China.
Wenchun
W
Xu
Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education Chongqing Medical University, 400016, Chongqing, China.
Liang
L
Zhong
Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education Chongqing Medical University, 400016, Chongqing, China.
Jian
J
Wang
Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education Chongqing Medical University, 400016, Chongqing, China.
Yibing
Y
Yin
Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education Chongqing Medical University, 400016, Chongqing, China. Electronic address: apoe@163.com.
Xuemei
X
Zhang
Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education Chongqing Medical University, 400016, Chongqing, China. Electronic address: wanghongljf@cqmu.edu.cn.
Hong
H
Wang
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D050956:HSP40 Heat-Shock Proteins / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D000067996:RAW 264.7 Cells; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity*; D014774:Virulence / Q000276:immunology*
D001426:Bacterial Proteins; D050956:HSP40 Heat-Shock Proteins; D019869:Phosphatidylinositol 3-Kinases
DnaJ; IL-6; JNK; PI3K; Streptococcus pneumoniae