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2017 ; 7
(1
): 11258
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Predicted effects of observed changes in the mRNA and microRNA transcriptome of
lung neutrophils during S pneumoniae pneumonia in mice
#MMPMID28900269
Gomez JC
; Dang H
; Kanke M
; Hagan RS
; Mock JR
; Kelada SNP
; Sethupathy P
; Doerschuk CM
Sci Rep
2017[Sep]; 7
(1
): 11258
PMID28900269
show ga
The complex role of neutrophils in modulating the inflammatory response is
increasingly appreciated. Our studies profiled the expression of mRNAs and
microRNAs (miRs) in lung neutrophils in mice during S. pneumoniae pneumonia and
performed in depth in silico analyses. Lung neutrophils were isolated 24?hours
after intratracheal instillation of PBS or S. pneumoniae, and differentially
expressed (DE) mRNAs and miRs were identified. Lung neutrophils from mice with S.
pneumoniae pneumonia contained 4127 DE mRNAs, 36% of which were upregulated at
least 2-fold. During pneumonia, lung neutrophils increase expression of pattern
recognition receptors, receptors for inflammatory mediators, transcription
factors including NF-?B and AP-1, Nrf2 targets, cytokines, chemokines and other
inflammatory mediators. Interestingly, neutrophils responded to Type I
interferons, whereas they both produced and responded to Type II interferon.
Expression of regulators of the inflammatory and immune response was verified at
the mRNA and protein level. Of approximately 1100 miRs queried, 31 increased and
67 decreased more than 2-fold in neutrophils from S. pneumoniae pneumonia.
Network analyses of potential DE miR-target DE mRNA interactions revealed
candidate key regulatory miRs. Thus, S. pneumoniae modulates mRNA and miR
expression by lung neutrophils, increasing their ability to respond and
facilitating host defense.