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Published on: January 17, 2014
IL-4 plays an essential role in DnaJ-ΔA146Ply-mediated immunoprotection against Streptococcus pneumoniae in mice
Yi Hu1, Lian Li1, Wenchun Xu1
1Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China.
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.
Insights
Interleukin-4 (IL-4) is crucial for the fusion protein DnaJ-ΔA146Ply
Area of Science:
- Immunology
- Microbiology
- Vaccine Development
Background:
- The fusion protein DnaJ-ΔA146Ply demonstrates protective effects against pneumococcal infections.
- Interleukin-4 (IL-4) deficient mice exhibit reduced survival and increased bacterial loads post-immunization, suggesting a role for IL-4 in DnaJ-ΔA146Ply-mediated immunity.
Purpose of the Study:
- To investigate the specific role of IL-4 in the protective immunity conferred by the DnaJ-ΔA146Ply fusion protein.
- To elucidate the mechanisms by which IL-4 influences cellular and humoral immune responses against pneumococcal challenge.
Main Methods:
- Comparative analysis of survival rates, bacterial loads, and antibody titers between wild-type (WT) and IL-4 knockout (IL-4-/-) mice immunized with DnaJ-ΔA146Ply.
- Assessment of passive immunization efficacy and bacterial clearance capacity of serum from immunized mice.
- Evaluation of neutrophil phagocytosis, Syk signaling pathway activation, and splenocyte cytokine production (IFN-γ, IL-17A) in WT and IL-4-/- mice.
Main Results:
- No significant differences in antibody titers were observed between WT and IL-4-/- mice.
- IL-4 deficiency impaired DnaJ-ΔA146Ply-dependent neutrophil phagocytosis, linked to reduced Syk and phosphor-Syk levels.
- Splenocytes from IL-4-/- mice produced higher levels of IFN-γ and IL-17A compared to WT mice.
Conclusions:
- IL-4 deficiency impacts the cellular immune response to DnaJ-ΔA146Ply, not antibody production or efficacy.
- IL-4 enhances antibody-dependent neutrophil phagocytosis, partly via Syk activation, contributing to protective immunity against pneumococcal infections.
- These findings highlight IL-4's critical role in cellular immunity for vaccine effectiveness.
