Dysfunctional cftr alters the bactericidal activity of human macrophages against pseudomonas aeruginosa

Paolal del Porto, Noemi Cifani, Simone Guarnieri, Enea Gino Di Domenico, Maria A. Mariggiò, Francesca Spadaro, Silvia Guglietta, Marco Anile, Federico Venuta, Serena Quattrucci, Fiorentina Ascenzioni

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Abstract

Chronic inflammation of the lung, as a consequence of persistent bacterial infections by several opportunistic pathogens represents the main cause of mortality and morbidity in cystic fibrosis (CF) patients. Mechanisms leading to increased susceptibility to bacterial infections in CF are not completely known, although the involvement of cystic fibrosis transmembrane conductance regulator (CFTR) in microbicidal functions of macrophages is emerging. Tissue macrophages differentiate in situ from infiltrating monocytes, additionally, mature macrophages from different tissues, although having a number of common activities, exhibit variation in some molecular and cellular functions. In order to highlight possible intrinsic macrophage defects due to CFTR dysfunction, we have focused our attention on in vitro differentiated macrophages from human peripheral blood monocytes. Here we report on the contribution of CFTR in the bactericidal activity against Pseudomonas aeruginosa of monocyte derived human macrophages. At first, by real time PCR, immunofluorescence and patch clamp recordings we demonstrated that CFTR is expressed and is mainly localized to surface plasma membranes of human monocyte derived macrophages (MDM) where it acts as a cAMP-dependent chloride channel. Next, we evaluated the bactericidal activity of P. aeruginosa infected macrophages from healthy donors and CF patients by antibiotic protection assays. Our results demonstrate that control and CF macrophages do not differ in the phagocytic activity when infected with P. aeruginosa. Rather, although a reduction of intracellular live bacteria was detected in both non-CF and CF cells, the percentage of surviving bacteria was significantly higher in CF cells. These findings further support the role of CFTR in the fundamental functions of innate immune cells including eradication of bacterial infections by macrophages.

Original languageEnglish
Article numbere19970
JournalPLoS One
Volume6
Issue number5
DOIs
Publication statusPublished - 2011

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

del Porto, P., Cifani, N., Guarnieri, S., Di Domenico, E. G., Mariggiò, M. A., Spadaro, F., Guglietta, S., Anile, M., Venuta, F., Quattrucci, S., & Ascenzioni, F. (2011). Dysfunctional cftr alters the bactericidal activity of human macrophages against pseudomonas aeruginosa. PLoS One, 6(5), [e19970]. https://doi.org/10.1371/journal.pone.0019970