The prototypic long pentraxin PTX3, a soluble pattern recognition receptor, plays an important role in innate defense against selected pathogens, by favoring their elimination and the initiation of protective responses. PTX3 has notably beneficial effects in mice infected with Aspergillus fumigatus and Pseudomonas aeruginosa. Cystic fibrosis (CF), a severe inherited autosomal recessive disease, is characterized by recurrent lung infections, especially by these two pathogens. We thus hypothesized that the status of PTX3 may be altered in CF patients. The levels and integrity of PTX3 were analyzed in the sputum samples from 51 CF patients and 7 patients with chronic obstructive pulmonary disease (COPD). The levels of PTX3 were increased in serums from CF and COPD patients, compared to healthy subjects, reflecting their infectious status. Surprisingly, the levels of PTX3 in sputum samples were dramatically lower in CF patients than in COPD patients. The low concentrations of PTX3 resulted from a proteolysis cleavage by elastase and Aspergillus fumigatus proteases. Interestingly, the N-terminal domain of PTX3, involved in the protection against Aspergillus fumigatus, is preferentially degraded by these proteases. These results indicate that the selective proteolysis of PTX3 in the CF lung may explain, at least in part, the recurrent lung infections by PTX3-sensitive pathogens in CF patients.
