| First Author | Wang X | Year | 2018 |
| Journal | Infect Immun | Volume | 86 |
| Issue | 3 | PubMed ID | 29229733 |
| Mgi Jnum | J:273571 | Mgi Id | MGI:6282762 |
| Doi | 10.1128/IAI.00651-17 | Citation | Wang X, et al. (2018) Expression of Toll-Like Receptor 2 by Dendritic Cells Is Essential for the DnaJ-DeltaA146Ply-Mediated Th1 Immune Response against Streptococcus pneumoniae. Infect Immun 86(3) |
| abstractText | The fusion protein DnaJ-DeltaA146Ply could induce cross-protective immunity against pneumococcal infection via mucosal and subcutaneous immunization in mice in the absence of additional adjuvants. DnaJ and Ply are both Toll-like receptor 4 (TLR4) but not TLR2 ligands. However, we found that TLR2(-/-) mice immunized subcutaneously with DnaJ-DeltaA146Ply showed significantly lower survival rates and higher bacterial loads in nasal washes than did wild-type (WT) mice after being challenged with pneumococcal strain D39 or 19F. The gamma interferon (IFN-gamma) level in splenocytes decreased in TLR2(-/-) mice, indicating that Th1 immunity elicited by DnaJ-DeltaA146Ply was impaired in these mice. We explored the mechanism of protective immunity conferred by DnaJ-DeltaA146Ply and the role of TLR2 in this process. DnaJ-DeltaA146Ply effectively promoted dendritic cell (DC) maturation via TLR4 but not the TLR2 signaling pathway. In a DnaJ-DeltaA146Ply-treated DC and naive CD4(+) T cell coculture system, the deficiency of TLR2 in DCs resulted in a significant decline of IFN-gamma production and Th1 subset differentiation. The same effect was observed in adoptive-transfer experiments. In addition, TLR2(-/-) DCs showed remarkably lower levels of the Th1-polarizing cytokine IL-12p70 than did WT DCs, suggesting that TLR2 was indispensable for DnaJ-DeltaA146Ply-induced IL-12 production and Th1 proliferation. Thus, our findings illustrate that dendritic cell expression of TLR2 is essential for optimal Th1 immune response against pneumococci in mice immunized subcutaneously with DnaJ-DeltaA146Ply. |
