Impairment of host defence by exotoxin A in Pseudomonas aeruginosa pneumonia in mice

Exotoxin A (P-ExA) is considered to be a major virulence factor of Pseudomo nas aeruginosa. Neutrophils, cytokines and nitric oxide (NO) have been impl icated as important components of an effective host defence against bacteri al respiratory tract infection. To study the role of P-ExA in the pathogene sis of P. aeruginosa pneumonia, C57Bl/6 mice were inoculated intranasally w ith wild-type PA103 or a mutant P. aeruginosa strain that did not produce P -ExA, PA103-29. P-ExA facilitated the outgrowth of P. aeruginosa in lungs, as reflected by an increasing number of cfu during pneumonia with strain PA 103, whereas the number of cfu decreased during pulmonary infection with st rain PA103-29. Influx of neutrophils was similar in broncho-alveolar lavage fluids (BALF) during pneumonia with strains PA103 and PA103-29. Lung level s of cytokines (tumor necrosis factor-alpha, interleukin-6) and chemokines (macrophage inflammatory protein-2, KC) were higher in mice inoculated with strain PA103, whereas BALF concentrations of NO were similar in mice treat ed with strains PA103 and PA103-29. These data suggest that P-ExA impairs h ost defence during pneumonia caused by P aeruginosa by a mechanism that doe s not involve effects on neutrophil influx, cytokines, chemokines or NO for mation.