Th17 cells are associated with protection from ventilator associated pneumonia.

Abstract

CD4+ T-helper 17 (Th17) cells and Interleukin (IL)-17A play an important role in clearing pathogens in mouse models of pneumonia. We hypothesized that numbers of Th17 cells and levels of IL-17A are associated with risk for nosocomial pneumonia in humans.We collected bronchoalveolar lavage (BAL) fluid from mechanically ventilated (n = 25) patients undergoing quantitative bacterial culture to evaluate for ventilator associated pneumonia (VAP). We identified Th17 cells by positive selection of CD4+ cells, stimulation with ionomycin and PMA, then staining for CD4, CD45, CCR6, IL-17A, and IFN-γ followed by flow cytometric analysis (n = 21). We measured inflammatory cytokine levels, including IL-17A, in BAL fluid by immunoassay.VAP was detected in 13 of the 25 subjects. We identified a decreased percentage of IL-17A producing Th17 cells in BAL fluid from patients with VAP compared to those without (p = 0.02). However, we found no significant difference in levels of IL-17A in patients with VAP compared to those without (p = 0.07). Interestingly, IL-17A levels did not correlate with Th17 cell numbers. IL-17A levels did show strong positive correlations with alveolar neutrophil numbers and total protein levels.Th17 cells are found at lower percentages in BAL fluid from mechanically ventilated patients with VAP and IL-17A levels correlated with Th17 cell percentages in non-VAP subjects, but not those with VAP. These findings suggest that Th17 cells may be protective against development of nosocomial pneumonia in patients receiving mechanical ventilation and that alveolar IL-17A in VAP may be derived from sources other than alveolar Th17 cells.