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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Host resistance to intranasal Acinetobacter baumannii reinfection in mice
Hongyu Qiu1, Zack Li1, Rhonda KuoLee1
1Human Health Therapeutics, National Research Council Canada, 100 Sussex Drive, Ottawa, ON K1A 0R6, Canada.
Abstract:
Acinetobacter baumannii is a major causative agent of healthcare-associated infection and develops multidrug resistance rapidly. However, little is known in the host defense mechanisms against this infection. In this study, we examined if mice recovered from a previous intranasal A. baumannii infection (recovered mice) are fully protected against a subsequent reinfection. We found that, despite the presence of specific serum IgG and mucosal IgA responses prior to the reinfection, the recovered mice were only marginally better protected against intranasal challenge with low doses of homologous or heterologous A. baumannii strains than the naïve mice. Post-challenge immune and inflammatory (cells and cytokines) responses were generally comparable between recovered and naïve mice although the recovered mice produced significantly higher amounts of IFN-γ and IL-17 and had higher percentages and numbers of resident lung CD44(hi)CD62L(-)CD4(+) and CD19(+) B lymphocytes. Taken together, our results suggest that mice recovered from a previous A. baumannii infection remain susceptible to reinfection, indicating the complexity of immune protection mechanism for this Gram-negative, multidrug-resistant emerging pathogen.
Insights
Mice previously infected with Acinetobacter baumannii showed limited protection against reinfection. Host immune responses were similar, indicating complex immunity against this multidrug-resistant pathogen.
Area of Science:
- Infectious Diseases
- Immunology
- Microbiology
Background:
- Acinetobacter baumannii is a significant cause of hospital-acquired infections.
- Rapid development of multidrug resistance in A. baumannii poses a major clinical challenge.
- Understanding host defense mechanisms against A. baumannii is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate the protective immunity conferred by a prior Acinetobacter baumannii infection against subsequent challenge.
- To compare the immune and inflammatory responses in previously infected versus naive mice upon reinfection.
Main Methods:
- Mice were intranasally inoculated with A. baumannii and allowed to recover.
- Recovered mice were subsequently challenged with homologous or heterologous A. baumannii strains.
- Immune responses, including serum IgG, mucosal IgA, cytokine levels, and lymphocyte populations (CD4+ T cells, CD19+ B cells), were analyzed.
Main Results:
- Recovered mice exhibited only marginal protection against reinfection compared to naive mice.
- Specific serum IgG and mucosal IgA responses were present in recovered mice prior to challenge.
- While overall immune responses were comparable, recovered mice showed higher IFN-γ and IL-17 production and increased resident lung CD4+ T and B lymphocytes.
Conclusions:
- Previous A. baumannii infection does not confer full protection against reinfection in mice.
- The immune protection mechanism against this Gram-negative, multidrug-resistant pathogen is complex.
- Further research is needed to elucidate the intricate host defense strategies against Acinetobacter baumannii.
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