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. Epub 2022 Feb 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • Bacterial Infections / immunology
  • Bacterial Load
  • Female
  • HSP40 Heat-Shock Proteins / genetics*
  • Immunity
  • Immunization
  • Inflammation / pathology
  • Interferon-gamma / metabolism
  • Interleukin-4 / deficiency
  • Interleukin-4 / metabolism*
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mutation / genetics*
  • Neutralization Tests
  • Neutrophils / immunology
  • Phagocytosis
  • Pneumococcal Infections / immunology*
  • Pneumococcal Infections / microbiology*
  • Pneumococcal Infections / prevention & control
  • Streptococcus pneumoniae / physiology*
  • Syk Kinase / metabolism

Substances

  • HSP40 Heat-Shock Proteins
  • Interleukin-4
  • Interferon-gamma
  • Syk Kinase