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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Respir+Cell+Mol+Biol
2015 ; 52
(3
): 349-64
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Mechanisms of interferon-? production by neutrophils and its function during
Streptococcus pneumoniae pneumonia
#MMPMID25100610
Gomez JC
; Yamada M
; Martin JR
; Dang H
; Brickey WJ
; Bergmeier W
; Dinauer MC
; Doerschuk CM
Am J Respir Cell Mol Biol
2015[Mar]; 52
(3
): 349-64
PMID25100610
show ga
Bacterial pneumonia is a common public health problem associated with significant
mortality, morbidity, and cost. Neutrophils are usually the earliest leukocytes
to respond to bacteria in the lungs. Neutrophils rapidly sequester in the
pulmonary microvasculature and migrate into the lung parenchyma and alveolar
spaces, where they perform numerous effector functions for host defense. Previous
studies showed that migrated neutrophils produce IFN-? early during pneumonia
induced by Streptococcus pneumoniae and that early production of IFN-? regulates
bacterial clearance. IFN-? production by neutrophils requires Rac2, Hck/Lyn/Fgr
Src family tyrosine kinases, and NADPH oxidase. Our current studies examined the
mechanisms that regulate IFN-? production by lung neutrophils during acute S.
pneumoniae pneumonia in mice and its function. We demonstrate that IFN-?
production by neutrophils is a tightly regulated process that does not require
IL-12. The adaptor molecule MyD88 is critical for IFN-? production by
neutrophils. The guanine nucleotide exchange factor CalDAG-GEFI modulates IFN-?
production. The CD11/CD18 complex, CD44, Toll-like receptors 2 and 4, TRIF, and
Nrf2 are not required for IFN-? production by neutrophils. The recently described
neutrophil-dendritic cell hybrid cell, identified by its expression of Ly6G and
CD11c, is present at low numbers in pneumonic lungs and is not a source of IFN-?.
IFN-? produced by neutrophils early during acute S. pneumoniae pneumonia induces
transcription of target genes in the lungs, which are critical for host defense.
These studies underline the complexity of the neutrophil responses during
pneumonia in the acute inflammatory response and in subsequent resolution or
initiation of immune responses.
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