Natural antibodies mediate resistance to <i>Acinetobacter baumannii</i>respiratory infections.

Abstract Acinetobacter baumanniiis a growing public health threat due to increasing incidence of carbapenem-resistant strains in U.S. hospitals. With widespread antibiotic resistance, there is an urgent need for alternative therapies treat these infections, which are often acquired hospital intensive care units. Antibody-based immunotherapies offer one potential treatment avenue, however, adaptive immune responses A. baumanniihave not been well characterized. Pilot experiments, using mouse pneumonia model explore the role immunity clearing baumannii, uncovered unexpected and severe defect resistance baumanniiinfection Rag2−/-mice during first 48 hours after infection. Subsequent experiments showed that intranasally infected Rag2−/−or B cell-deficient μMT mice impaired compared wild type bacteria from lung, liver, spleen at 24 post Prophylactic administration normal serum or purified immunoglobulins naive demonstrates protective effect natural antibodies (NAbs) by rescuing Rag2−/−mice Analysis C3 complement protein binding demonstrated NAbs increased deposition on baumanniicells, indicating activation classical pathway as mechanism action. Overall, our study previously unknown innate Acinetobacterpneumonia, finding may lead development effective against human infections caused this antibiotic-resistant pathogen.