TY - JOUR
T1 - The B lymphocyte differentiation factor (BAFF) is expressed in the airways of children with CF and in lungs of mice infected with Pseudomonas aeruginosa
AU - Neill, Daniel R.
AU - Saint, Gemma L.
AU - Bricio-Moreno, Laura
AU - Fothergill, Joanne L.
AU - Southern, Kevin W.
AU - Winstanley, Craig
AU - Christmas, Stephen E.
AU - Slupsky, Joseph R.
AU - McNamara, Paul S.
AU - Kadioglu, Aras
AU - Flanagan, Brian F.
PY - 2014/5/21
Y1 - 2014/5/21
N2 - Background: Chronic lung infection with Pseudomonas aeruginosa remains a major cause of mortality and morbidity among individuals with CF. Expression of mediators promoting recruitment and differentiation of B cells, or supporting antibody production is poorly understood yet could be key to controlling infection.Methods: BAFF was measured in BAL from children with CF, both with and without P. aeruginosa, and controls. Mice were intra-nasally infected with P. aeruginosa strain LESB65 for up to 7 days. Cellular infiltration and expression of B cell chemoattractants and B cell differentiation factor, BAFF were measured in lung tissue.Results: BAFF expression was elevated in both P. aeruginosa negative and positive CF patients and in P. aeruginosa infected mice post infection. Expression of the B cell chemoattractants CXCL13, CCL19 and CCL21 increased progressively post infection.Conclusions: In a mouse model, infection with P. aeruginosa was associated with elevated expression of BAFF and other B cell chemoattractants suggesting a role for airway B cell recruitment and differentiation in the local adaptive immune response to P. aeruginosa. The paediatric CF airway, irrespective of pseudomonal infection, was found to be associated with an elevated level of BAFF implying that BAFF expression is not specific to pseudomonas infection and may be a feature of the CF airway. Despite the observed presence of a potent B cell activator, chronic colonisation is common suggesting that this response is ineffective.
AB - Background: Chronic lung infection with Pseudomonas aeruginosa remains a major cause of mortality and morbidity among individuals with CF. Expression of mediators promoting recruitment and differentiation of B cells, or supporting antibody production is poorly understood yet could be key to controlling infection.Methods: BAFF was measured in BAL from children with CF, both with and without P. aeruginosa, and controls. Mice were intra-nasally infected with P. aeruginosa strain LESB65 for up to 7 days. Cellular infiltration and expression of B cell chemoattractants and B cell differentiation factor, BAFF were measured in lung tissue.Results: BAFF expression was elevated in both P. aeruginosa negative and positive CF patients and in P. aeruginosa infected mice post infection. Expression of the B cell chemoattractants CXCL13, CCL19 and CCL21 increased progressively post infection.Conclusions: In a mouse model, infection with P. aeruginosa was associated with elevated expression of BAFF and other B cell chemoattractants suggesting a role for airway B cell recruitment and differentiation in the local adaptive immune response to P. aeruginosa. The paediatric CF airway, irrespective of pseudomonal infection, was found to be associated with an elevated level of BAFF implying that BAFF expression is not specific to pseudomonas infection and may be a feature of the CF airway. Despite the observed presence of a potent B cell activator, chronic colonisation is common suggesting that this response is ineffective.
KW - Animals
KW - B-Cell Activating Factor/metabolism
KW - Case-Control Studies
KW - Chemokine CCL19/metabolism
KW - Chemokine CCL21/metabolism
KW - Chemokine CXCL13/metabolism
KW - Child
KW - Cystic Fibrosis/immunology
KW - Female
KW - Humans
KW - Lung/metabolism
KW - Mice, Inbred BALB C
KW - Pseudomonas Infections/immunology
KW - Pseudomonas aeruginosa/immunology
U2 - 10.1371/journal.pone.0095892
DO - 10.1371/journal.pone.0095892
M3 - Article
C2 - 24847941
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 5
M1 - e95892
ER -