RT Journal Article
SR Electronic
T1 A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 985
OP 992
DO 10.1136/thoraxjnl-2012-201591
VO 67
IS 11
A1 Helen M Marriott
A1 Marc Daigneault
A1 Alfred A R Thompson
A1 Sarah R Walmsley
A1 Sharonjit K Gill
A1 Derrick R Witcher
A1 Victor J Wroblewski
A1 Paul G Hellewell
A1 Moira K B Whyte
A1 David H Dockrell
YR 2012
UL http://thorax.bmj.com/content/67/11/985.abstract
AB Background Therapeutic strategies to modulate the host response to bacterial pneumonia are needed to improve outcomes during community-acquired pneumonia. This study used mice with impaired Fas signalling to examine susceptibility to pneumococcal pneumonia and decoy receptor 3 analogue (DcR3-a) to correct factors associated with increased susceptibility. Methods Wild-type mice and those with varying degrees of impairment of Fas (lpr) or Fas ligand signalling (gld) were challenged with Streptococcus pneumoniae and microbiological and immunological outcomes measured in the presence or absence of DcR3-a. Results During established pneumonia, neutrophils became the predominant cell in the airway and gld mice were less able to clear bacteria from the lungs, demonstrating localised impairment of pulmonary neutrophil function in comparison to lpr or wild-type mice. T-cells from gld mice had enhanced activation and reduced apoptosis in comparison to wild-type and lpr mice during established pneumonia. Treatment with DcR3-a reduced T-cell activation and corrected the defect in pulmonary bacterial clearance in gld mice. Conclusions The results suggest that imbalance in tumour necrosis factor superfamily signalling and excessive T-cell activation can impair bacterial clearance in the lung but that DcR3-a treatment can reduce T-cell activation, restore optimal pulmonary neutrophil function and enhance bacterial clearance during S pneumoniae infection.