Collaboration between macrophages and vaccine-induced CD4 T cells confers protection against lethal Pseudomonas aeruginosa pneumonia during neutropenia.

Channing Laboratory, Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
The Journal of Infectious Diseases (Impact Factor: 5.85). 10/2012; DOI: 10.1093/infdis/jis657
Source: PubMed

ABSTRACT The utility of vaccine-based strategies to prevent lethal bacterial infection in a host with neutropenia is not well defined. Here, we show in a neutropenic mouse model that immunity induced by mucosal vaccination with a live-attenuated P. aeruginosa vaccine is protective against lethal P. aeruginosa pneumonia caused by both vaccine-homologous and -heterologous strains, whereas passive immunization confers only vaccine-homologous protection. Cells in the macrophage-lineage served as crucial innate cellular effectors in the neutropenic host after active immunization. Vaccine efficacy was CD4 T cell-dependent and associated with post-infectious accumulation of macrophage-lineage cells in the alveolar space as well as enhanced P. aeruginosa clearance from the lung. Adaptive CD4 T cells produced GM-CSF upon re-stimulation in vitro, and local GM-CSF was critical for vaccine efficacy. Thus, collaboration between the innate and adaptive effectors induced by mucosal vaccination can overcome neutropenia and confer protection against lethal bacterial infection in the profoundly neutropenic host.

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