PMID- 25706389
OWN - NLM
STAT- MEDLINE
DCOM- 20151229
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 2
DP  - 2015
TI  - Granulocyte-macrophage colony stimulatory factor enhances the pro-inflammatory 
      response of interferon-gamma-treated macrophages to Pseudomonas aeruginosa infection.
PG  - e0117447
LID - 10.1371/journal.pone.0117447 [doi]
LID - e0117447
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe 
      infections at compromised epithelial surfaces, such those found in burns, wounds, 
      and in lungs damaged by mechanical ventilation or recurrent infections, 
      particularly in cystic fibrosis (CF) patients. CF patients have been proposed to 
      have a Th2 and Th17-biased immune response suggesting that the lack of Th1 and/or 
      over exuberant Th17 responses could contribute to the establishment of chronic P. 
      aeruginosa infection and deterioration of lung function. Accordingly, we have 
      observed that interferon (IFN)-gamma production by peripheral blood mononuclear cells 
      from CF patients positively correlated with lung function, particularly in 
      patients chronically infected with P. aeruginosa. In contrast, IL-17A levels 
      tended to correlate negatively with lung function with this trend becoming 
      significant in patients chronically infected with P. aeruginosa. These results 
      are in agreement with IFN-gamma and IL-17A playing protective and detrimental roles, 
      respectively, in CF. In order to explore the protective effect of IFN-gamma in CF, 
      the effect of IFN-gamma alone or in combination with granulocyte-macrophage 
      colony-stimulating factor (GM-CSF), on the ability of human macrophages to 
      control P. aeruginosa growth, resist the cytotoxicity induced by this bacterium 
      or promote inflammation was investigated. Treatment of macrophages with IFN-gamma, in 
      the presence and absence of GM-CSF, failed to alter bacterial growth or 
      macrophage survival upon P. aeruginosa infection, but changed the inflammatory 
      potential of macrophages. IFN-gamma caused up-regulation of monocyte chemoattractant 
      protein-1 (MCP-1) and TNF-alpha and down-regulation of IL-10 expression by infected 
      macrophages. GM-CSF in combination with IFN-gamma promoted IL-6 production and 
      further reduction of IL-10 synthesis. Comparison of TNF-alpha vs. IL-10 and IL-6 vs. 
      IL-10 ratios revealed the following hierarchy in regard to the pro-inflammatory 
      potential of human macrophages infected with P. aeruginosa: untreated < treated 
      with GM-CSF < treated with IFN-gamma < treated with GM-CSF and IFN-gamma.
FAU - Singh, Sonali
AU  - Singh S
AD  - School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, United 
      Kingdom.
FAU - Barr, Helen
AU  - Barr H
AD  - School of Medicine, University of Nottingham, Nottingham, NG7 2RD, United 
      Kingdom.
FAU - Liu, Yi-Chia
AU  - Liu YC
AD  - School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, United 
      Kingdom.
FAU - Robins, Adrian
AU  - Robins A
AD  - School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, United 
      Kingdom.
FAU - Heeb, Stephan
AU  - Heeb S
AD  - School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, United 
      Kingdom.
FAU - Williams, Paul
AU  - Williams P
AD  - School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, United 
      Kingdom.
FAU - Fogarty, Andrew
AU  - Fogarty A
AD  - School of Community Health Sciences, University of Nottingham, Nottingham, NG7 
      2RD, United Kingdom.
FAU - Camara, Miguel
AU  - Camara M
AD  - School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, United 
      Kingdom.
FAU - Martinez-Pomares, Luisa
AU  - Martinez-Pomares L
AD  - School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, United 
      Kingdom.
LA  - eng
GR  - G0801558/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150223
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytokines)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cystic Fibrosis/metabolism/microbiology
MH  - Cytokines/metabolism
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*metabolism
MH  - Humans
MH  - Inflammation/metabolism
MH  - Interferon-gamma/*metabolism
MH  - Macrophages/*metabolism/microbiology
MH  - Male
MH  - Pseudomonas Infections/*metabolism
MH  - Pseudomonas aeruginosa/growth & development/*physiology
MH  - Young Adult
PMC - PMC4338139
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/02/24 06:00
MHDA- 2015/12/30 06:00
PMCR- 2015/02/23
CRDT- 2015/02/24 06:00
PHST- 2014/03/12 00:00 [received]
PHST- 2014/12/23 00:00 [accepted]
PHST- 2015/02/24 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2015/12/30 06:00 [medline]
PHST- 2015/02/23 00:00 [pmc-release]
AID - PONE-D-14-11230 [pii]
AID - 10.1371/journal.pone.0117447 [doi]
PST - epublish
SO  - PLoS One. 2015 Feb 23;10(2):e0117447. doi: 10.1371/journal.pone.0117447. 
      eCollection 2015.