Alveolar macrophage apoptosis contributes to pneumococcal clearance in a resolving model of pulmonary infection.
The role of alveolar macrophages (AM) in host defense against pulmonary infection has been difficult to establish using in vivo models. This may reflect a reliance on models of fulminant infection. To establish a unique model of resolving infection, with which to address the function of AM, C57BL/6 mice received low-dose intratracheal administration of pneumococci. Administration of low doses of pneumococci produced a resolving model of pulmonary infection characterized by clearance of bacteria without features of pneumonia. AM depletion in this model significantly increased bacterial outgrowth in the lung. Interestingly, a significant increase in the number of apoptotic AM was noted with the low-dose infection as compared with mock infection. Caspase inhibition in this model decreased AM apoptosis and increased the number of bacteremic mice, indicating a novel role for caspase activation in pulmonary innate defense against pneumococci. These results suggest that AM play a key role in clearance of bacteria from the lung during subclinical infection and that induction of AM apoptosis contributes to the microbiologic host defense against pneumococci.
Dockrell
David H
DH
Division of Genomic Medicine, University of Sheffield School of Medicine and Biomedical Sciences, Sheffield, United Kingdom. d.h.dockrell@sheffield.ac.uk
Marriott
Helen M
HM
Prince
Lynne R
LR
Ridger
Victoria C
VC
Ince
Paul G
PG
Hellewell
Paul G
PG
Whyte
Moira K B
MK
D000590:Amino Acid Chloromethyl Ketones / Q000008:administration & dosage; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D016470:Bacteremia / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D061945:Caspase Inhibitors; D002452:Cell Count; D015853:Cysteine Proteinase Inhibitors / Q000008:administration & dosage; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D007442:Intubation, Intratracheal; D016676:Macrophages, Alveolar / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011018:Pneumonia, Pneumococcal / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone