Chemotherapy drugs can kill infection-fighting white blood cells called neutrophils in the bone marrows of cancer patients, raising the risk of life-threatening infections.
Researchers tested whether a live attenuated vaccine against Pseudomonas aeruginosa protects mice treated with the chemotherapy drug cyclophosphamide against bacterial pneumonia. Compared with unvaccinated mice, mice that were administered three weekly intranasal doses of the vaccine exhibited significantly reduced bacterial load in the lungs following exposure to P. aeruginosa and three doses of cyclophosphamide—despite patent chemotherapy-induced depletion of neutrophils.
Further experiments revealed that the vaccine triggers the expansion of a previously unreported group of activated lung macrophages that survive chemotherapy and confer protection against pneumonia.
When the authors purified the vaccine-induced macrophages and transferred them into the tracheas of unvaccinated mice exposed to cyclophosphamide and P. aeruginosa, the cells prolonged the survival of the neutrophil-depleted mice. Further, T cells, but not antibodies, contributed to vaccine-induced protection against the bacterial pathogen.
The findings unearth a reserve of lung immune cells that could be activated by vaccination to confer protection against chemotherapy-induced bone marrow damage and infections. According to the authors, pinpointing the macrophage-boosting components of the vaccine could pave the way toward a safe and effective candidate vaccine against lung infection in immune-compromised cancer patients.
http://www.pnas.org/content/113/41/E6153
Vaccine protects mice against chemotherapy-induced lung infection
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