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Characterization of a cyclophosphamide-induced murine model of immunosuppression to study Acinetobacter baumannii
Swetha Manepalli1, Jay A Gandhi1, Vaibhav V Ekhar1
1Department of Biomedical Sciences, Long Island University-Post, Brookville, NY, USA.
Abstract:
Acinetobacter baumannii is a Gram-negative bacterium that opportunistically infects critically ill hospitalized patients with breaches in skin integrity and airway protection, leading to significant morbidity and mortality. Considering the paucity of well-established animal models of immunosuppression to study A. baumannii pathogenesis, we set out to characterize a murine model of immunosuppression using the alkylating agent cyclophosphamide (CYP). We hypothesized that CYP-induced immunosuppression would increase the susceptibility of C57BL/6 mice to developing A. baumannii-mediated pneumonia followed by systemic disease. We demonstrated that CYP intensified A. baumannii-mediated pulmonary disease, abrogated normal immune cell function and led to altered pro-inflammatory cytokine release. The development of an animal model that mimics A. baumannii infection onset in immunosuppressed individuals is crucial for generating novel approaches to patient care and improving public health strategies to decrease exposure to infection for individuals at risk.
Insights
A new mouse model using cyclophosphamide (CYP) effectively mimics Acinetobacter baumannii infections in immunosuppressed patients. This model shows increased disease severity and altered immune responses, aiding research into critical care.
Area of Science:
- Bacteriology
- Immunology
- Infectious Diseases
Background:
- Acinetobacter baumannii is a critical Gram-negative pathogen causing severe infections in hospitalized patients.
- Effective animal models for studying A. baumannii in immunosuppressed states are limited.
- Such models are vital for understanding pathogenesis and developing treatments.
Purpose of the Study:
- To characterize a murine model of immunosuppression using cyclophosphamide (CYP) for studying A. baumannii.
- To assess the impact of CYP-induced immunosuppression on susceptibility to A. baumannii pneumonia and systemic infection.
Main Methods:
- C57BL/6 mice were treated with cyclophosphamide (CYP) to induce immunosuppression.
- Mice were subsequently infected with Acinetobacter baumannii.
- Pulmonary disease, immune cell function, and pro-inflammatory cytokine release were analyzed.
Main Results:
- CYP treatment significantly intensified A. baumannii-mediated pulmonary disease.
- Immunosuppression abrogated normal immune cell function.
- Altered pro-inflammatory cytokine release patterns were observed in infected, immunosuppressed mice.
Conclusions:
- The characterized murine model effectively mimics A. baumannii infection in immunosuppressed individuals.
- This model is crucial for developing novel patient care strategies and public health interventions.
- Further research using this model can improve outcomes for at-risk populations.