Phagocytic and signaling innate immune receptors: are they dysregulated in cystic fibrosis in the fight against Pseudomonas aeruginosa?

Abstract

Cystic fibrosis (CF) is a genetic disease that affects mainly the lung and the digestive system, causing progressive disability and organ failure. The most prevalent CFTR mutation dF508 (which constitutes 70% of all mutations) results in an incorrect targeting of the CFTR molecule to the membrane. It is now a well-accepted concept that mucosal innate immune responses are dysregulated in cystic fibrosis through a cycle of infectious and inflammatory episodes. However, although much work has focused on the late consequences of chronic lung inflammation in CF, very little is known on the early events leading to infection and colonization, such as that of Pseudomonas aeruginosa (P.a). We review here the involvement of a range of innate phagocytic/signaling receptors in the control of this pathogen (mannose receptor, complement receptor-3, Toll-like receptors, etc.) and evaluate the possibility that the activity of some of these receptors may be dysregulated in cystic fibrosis, potentially explaining the florid infections encountered in this disease.