Pneumococcal DnaJ modulates dendritic cell-mediated Th1 and Th17 immune responses through Toll-like receptor 4 signaling pathway |
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| Affiliation: | 1. College of Laboratory Medicine, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing 400016, China;2. Department of Laboratory Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000,China;1. Department of Toxicology, School of public health, Zhejiang University School of Medicine, Hangzhou 310058, China;2. Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China;3. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China;4. The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 31000, China;5. Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou 310000, China;6. Blood center of Zhejiang Province, Hangzhou 310000, China;1. Department of Paediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy;2. Department of Maternal and Children’s Health, Obstetrics and Gynecology Unit, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy;3. Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Italy;4. Department of Maternal and Children’s Health, Neonatal Intensive Care Unit, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy;1. Center for Innovation Competence, Humoral Immune Reactions in Cardiovascular Diseases, University Medicine Greifswald, 17489 Greifswald, Germany;2. Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, 17475 Greifswald, Germany;1. Servicio de Parasitología-Chagas, Hospital de Niños “Dr. Ricardo Gutiérrez”, Ciudad de Buenos Aires, Argentina;2. Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina;1. Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, 800 Rose Street Rm MS409, Lexington, KY 40536, USA;2. Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, 789 S. Limestone Street Suite 292, Lexington, KY 40536, USA;3. Department of Internal Medicine, University of Kentucky College of Medicine, 900 S. Limestone Street Suite 303, Lexington, KY 40536, USA |
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| Abstract: | 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. |
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| Keywords: | DnaJ Dendritic cell Th1 Th17 TLR4 MAPKs PI3K-Akt NF-κB |
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