Pneumococcal DnaJ modulates dendritic cell-mediated Th1 and Th17 immune responses through Toll-like receptor 4 signaling pathway.
Pneumococcal DnaJ was recently shown to be a potential protein vaccine antigen that induces strong Th1 and Th17 immune response against streptococcus pneumoniae infection in mice. However, how DnaJ mediates T cell immune response against S. pneumoniae infection has not been addressed. Here, we investigate whether DnaJ contributes to the development of T cell immunity through the activation of bone marrow-derived dendritic cells (BMDCs). We found that endotoxin-free recombinant DnaJ (rDnaJ) induced activation and maturation of BMDCs via recognition of Toll-like receptor 4 (TLR4) and activation of MAPKs, NF-κB and PI3K-Akt pathways. rDnaJ-treated BMDCs effectively stimulated naïve CD4+T cells to secrete IFN-γ and IL-17A. Splenocytes from mice that were adoptively transferred with rDnaJ-pulsed BMDCs secreted higher levels of IFN-γ and IL-17A compared with those that received PBS-activated BMDCs. Splenocytes from TLR4-/-mice immunized with rDnaJ produced lower levels of IFN-γ and IL-17A compared with those from wild type mice. Our findings indicate that DnaJ can induce Th1 and Th17 immune responses against S. pneumoniae through activation of BMDCs in a TLR4-dependent manner.
College of Laboratory Medicine, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing 400016, China; Department of Laboratory Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000,China.
Yingying
Y
Wu
College of Laboratory Medicine, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing 400016, China.
Jingjing
J
Cui
College of Laboratory Medicine, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing 400016, China.
Xuemei
X
Zhang
College of Laboratory Medicine, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing 400016, China.
Song
S
Gao
College of Laboratory Medicine, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing 400016, China.
Feng
F
Ma
College of Laboratory Medicine, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing 400016, China.
Hua
H
Yao
College of Laboratory Medicine, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing 400016, China.
Xiaoyu
X
Sun
College of Laboratory Medicine, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing 400016, China.
Yujuan
Y
He
College of Laboratory Medicine, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing 400016, China.
Yibing
Y
Yin
College of Laboratory Medicine, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing 400016, China. Electronic address: xuwen0303@126.com.
Wenchun
W
Xu
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology*; D050956:HSP40 Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D056747:Immunomodulation; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011008:Pneumococcal Infections / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000502:physiology*; D058504:Th17 Cells / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D001426:Bacterial Proteins; D015415:Biomarkers; D016207:Cytokines; D050956:HSP40 Heat-Shock Proteins; D016328:NF-kappa B; D022242:Pneumococcal Vaccines; D011994:Recombinant Proteins; D051197:Toll-Like Receptor 4; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
Dendritic cell; DnaJ; MAPKs; NF-κB; PI3K-Akt; S. pneumonia; TLR4; Th1; Th17