Th17 cells are associated with protection from ventilator associated pneumonia.

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.