Dipeptidyl peptidase I controls survival from Klebsiella pneumoniae lung infection by processing surfactant protein D

作者：Sutherland Rachel E; Barry Sophia S; Olsen Joanna S; Salantes D Brenda; Caughey George H; Wolters Paul J^*

来源：Biochemical and Biophysical Research Communications, 2014, 450(1): 818-823.

DOI：10.1016/j.bbrc.2014.06.062

• Bacterial killing
• Collectin
• Innate immunity
• Pulmonary inflammation

Prior work established that a deficiency in the cysteine protease dipeptidyl peptidase I (DPPI) improves survival following polymicrobial septic peritonitis. To test whether DPPI regulates survival from severe lung infections, DPPI-/- mice were studied in a Klebsiella pneumoniae lung infection model, finding that survival in DPPI-/- mice is significantly better than in DPPI+/+ mice 8 d after infection. DPPI-/- mice have significantly fewer bacteria in the lung than infected DPPI+/+ mice, but no difference in lung histopathology, lung injury, or cytokine levels. To explore mechanisms of enhanced bacterial clearance in DPPI-/- mice, we examined the status of pulmonary collectins, finding that levels of surfactant protein D, but not of surfactant protein A, are higher in DPPI-/- than in DPPI+/+ BAL fluid, and that DPPI-/- BAL fluid aggregate bacteria more effectively than control BAL fluid. Sequencing of the amino terminus of surfactant protein D revealed two or eight additional amino acids in surfactant protein D isolated from DPPI-/- mice, suggesting processing by DPPI. These results establish that DPPI is a major determinant of survival following Klebsiella pneumoniae lung infection and suggest that the survival disadvantage in DPPI+/+ mice is in part due to processing of surfactant protein D by DPPI.

• 出版日期2014-7-18