Essential Role of B Cells in Early Defense Against Acinetobacter baumannii Pulmonary Infections

Treatment of antibiotic-resistant Acinetobacter baumannii infections has become exceedingly challenging, leading to higher morbidity and mortality. Therefore, the development of new therapeutics to treat these infections is critically needed, and immunotherapy is one potential treatment option. Immune responses against this pathogen, particularly lymphocyte- mediated responses, are not well understood. In this study, we investigated the role of B cells in innate resistance to A. baumannii pulmonary infection using a B cell-deficient (µMT) mouse model. B cell-deficient mice were impaired in clearing A. baumannii from the lung, liver, and spleen and failed to prevent extrapulmonary dissemination of A. baumannii after infection. Transcriptomic analyses indicated that the lack of B cells was associated with reduced expression of several genes encoding antimicrobial proteins. In addition, B cell deficiency was associated with pulmonary eosinophilia and increased pulmonary recruitment of Ly6C ⁺ NK cells following A. baumannii infection. This study demonstrates the significant role of B cells in providing early protection against A. baumannii infection and implicates B cell-dependent mechanisms beyond antibody-mediated bacterial resistance.