Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene that codes for the cystic fibrosis trans-membrane conductance regulator. These mutations result in abnormal secretions viscous airways of the lungs, favoring pulmonary infection and inflammation in the middle of neutrophil recruitment. Recently it was described that neutrophils can contribute with disease pathology by extruding large amounts of nuclear material through a mechanism of cell death known as Neutrophil Extracellular Traps into the airways of patients with cystic fibrosis. Additionally, NETs production can contribute to airway colonization with bacteria, since they are the microorganisms most frequently found in these patients. In this review, we will discuss the implication of individual or mixed bacterial infections that most often colonize the lung of patients with cystic fibrosis, and the NETs role on the disease.

Cystic fibrosis (CF) is a disease characterized by bacterial chronic infection of the respiratory tract and inflammation, which leads to a progressive decrease in lung function. Pseudomonas aeruginosa is commonly isolated from the sputum of patients and their presence is associated with a predominant airway inflammation with neutrophils, causing chronic colonization and higher mortality rates. Neutrophil extracellular traps (NETs) have been observed in response against Pseudomonas, however, these cannot eliminate the pathogen from the respiratory tract, so one possibility is that the bacteria could promote their production to use them as a scaffold to colonize the lungs and as a nutrient source, however, their overproduction could also lead to increased damage to the lungs. In this work, we evaluated NETs formation by Pseudomonas clinical isolates obtained from CF patients and found that these induced NETs formation with globular or spread morphologies, of note, we found that there is a trend by which the spread forms were induced mainly by isolates obtained from patients with severe disease, whereas, the globular morphologies were observed for isolates obtained from patients with mild/moderate disease. Finally, we screened for bacterial molecules implicated in NETs formation and found that Exotoxin S, pyocin S2 and pyoverdine could participate in the process.

Neutrophils activated with pathogens or their products induce formation of extracellular traps (NETs), but if this constitutes a general response against all pathogenic species in a single genus or intrageneric differences exist remains unknown, yet this is of great importance for the establishment of effective treatments. To determine this, we analyzed neutrophil extracellular traps formation after the stimulation with bloodstream isolates from different Candida species (Candida albicans, C. tropicalis, C. parapsilosis, and C. glabrata), and found that each species has a different capacity to induce DNA extrusion, which is independent of their morphology (yeast or hyphae). We observed that phospholipase producer’s strains and their secretion products were able to induce NETs, a property not observed with phospholipase deficient strains, with exception of some Candida glabrata sensu stricto isolates, which showed no NETs induction although they did show phospholipase production. To further analyze this, we extended our study to include Candida glabrata cryptic species (C. bracarensis and C. nivariensis) and no extracellular traps formation was observed. Here, we contribute to the understanding of how neutrophils initiate NETs, and we found that certain strains may have a differential capacity to trigger these structures, which may explain the high mortality of some isolates.