Pneumococcal DnaJ modulates dendritic cell-mediated Th1 and Th17 immune responses through Toll-like receptor 4 signaling pathway.

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.

• Authors: Yingying Wu, Jingjing Cui, Xuemei Zhang, Song Gao, Feng Ma, Hua Yao, Xiaoyu Sun, Yujuan He, Yibing Yin, Wenchun Xu
• Journal: Immunobiology (Immunobiology) Vol. 222 Issue 2 Pg. 384-393 (02 2017) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 27594384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier GmbH. All rights reserved.

Chemical References

• Bacterial Proteins
• Biomarkers
• Cytokines
• HSP40 Heat-Shock Proteins
• NF-kappa B
• Pneumococcal Vaccines
• Recombinant Proteins
• Toll-Like Receptor 4
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Bacterial Proteins (immunology, metabolism)
• Biomarkers
• Cell Differentiation (immunology)
• Cytokines (metabolism)
• Dendritic Cells (cytology, physiology)
• HSP40 Heat-Shock Proteins (immunology, metabolism)
• Host-Pathogen Interactions (immunology)
• Immunomodulation
• Immunophenotyping
• Lymphocyte Activation (immunology)
• Mice
• Mice, Knockout
• NF-kappa B (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Pneumococcal Infections (prevention & control)
• Pneumococcal Vaccines (immunology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Recombinant Proteins (immunology, metabolism)
• Signal Transduction
• Streptococcus pneumoniae (immunology, metabolism)
• Th1 Cells (physiology)
• Th17 Cells (physiology)
• Toll-Like Receptor 4 (metabolism)