IL-4 plays an essential role in DnaJ-ΔA146Ply-mediated immunoprotection against Streptococcus pneumoniae in mice

  • Mol Immunol. 2022 Mar;143:105-113. doi: 10.1016/j.molimm.2022.01.010.
Yi Hu  1 ,  Lian Li  1 ,  Wenchun Xu  1 ,  Kaifeng Wu  2 ,  Jiangming Xiao  1 ,  Yang Peng  1 ,  Yusi Liu  3 ,  Yibing Yin  1 ,  Xuemei Zhang  4
Affiliations
  • 1. Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China.
  • 2. Department of Laboratory Medicine, the Third Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China.
  • 3. Department of Laboratory Medicine, the First Affiliated Hospital of China Medical University, Shenyang 110001, China.
  • 4. Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China. Electronic address: [email protected].
PMID: 35114487 DOI: 10.1016/j.molimm.2022.01.010
Abstract

The fusion protein DnaJ-ΔA146Ply is protective against pneumococcal infections in mice. However, we found that immunized IL-4-/- mice showed significant lower survival rates and higher Bacterial loads than did wild-type (WT) mice after being challenged. We explored the role of IL-4 in the protective immunity conferred by DnaJ-ΔA146Ply. Our results showed that there were no significant differences in antibody titers between immunized WT mice and IL-4-/- mice. The Bacterial loads of passively immunized IL-4-/- mice were significantly higher than those of WT mice, while mice immunized with anti-DnaJ-ΔA146Ply serum from WT and IL-4-/- mice showed similar capacity for Bacterial clearance. DnaJ-ΔA146Ply-dependent phagocytosis of IL-4-/- neutrophils was significant decreased compared with that of WT neutrophils. The levels of Syk and phosphor-Syk in IL-4-/- neutrophils were decreased compared with those in WT neutrophils. Additionally, Splenocytes in IL-4-/- mice triggered significantly higher levels of IFN-γ and IL-17A than did splenocytes in WT mice. Taken together, our findings illustrate that IL-4 deficiency does not influence the antibody production or antibody effect, but change the cellular immune response induced by DnaJ-ΔA146Ply. Additionally, IL-4 can enhance the antibody-dependent phagocytosis of neutrophils partially by activating Syk and participate in the protective immunity induced by DnaJ-ΔA146Ply.

Keywords
DnaJ-ΔA146Ply; IL-4; Protection; Streptococcus pneumoniae.
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