Decreased expression of HLA-DQ and HLA-DR on cells of the monocytic lineage in cystic fibrosis
- 493 Downloads
We studied HLA class II molecules on blood monocyte subsets, blood dendritic cells, sputum macrophages, and monocyte-derived macrophages at the protein (flow cytometry) and mRNA level (RT-PCR) in adult patients with cystic fibrosis (CF) and healthy control subjects as putative contributors to the CF phenotype. In healthy donors, we found a high average HLA-DQ expression of 4.35 mean specific fluorescence intensity units (ΔMnI) on classical blood monocytes. In F508del homozygous CF patients, the average ΔMnI was low (1.80). Patients were divided into two groups, in which 14 of these patients had HLA-DQ expression above 2 ΔMnI (average 3.25 ΔMnI, CF-DQgroup1) and 36 below (average 1.24 ΔMnI, CF-DQgroup2). Also, the CD16-positive monocyte subset and blood dendritic cells showed much lower levels of HLA-DQ for the CF-DQgroup2 patients compared with healthy controls. In macrophages from sputum and derived from monocytes, in vitro HLA-DQ expression was dramatically decreased to background levels in CF-DQgroup2. MHC class II transcripts were reduced in CF with a sevenfold decrease in HLA-DQβ1 for CF-DQgroup2 patients. Higher levels of the inflammation marker CRP were associated with low HLA-DQ protein expression, and in vitro treatment with the inflammatory molecule lipopolysaccharide reduced HLA-DQ expression. Interferon γ (IFNγ) could overcome this effect in healthy donor cells while, in CF, the IFNγ-induced activation was impaired. Our data demonstrate a pronounced reduction of HLA-DQ expression in CF, which is associated with inflammation and a reduced response to IFNγ.
• CF patients show a reduced expression of MHCII molecules in monocytes and macrophages.
• HLA-DQ and HLA-DR transcript levels are also reduced in CF patients.
• CF patient C-reactive protein levels correlate with low HLA-DQ expression.
• Reduced expression of MHC class II molecules appears to be linked to inflammation.
• CF patients exhibit an impaired response to IFNgamma.
KeywordsCystic fibrosis HLA-DQ HLA-DR Inflammation Monocytes, macrophages and dendritic cells
We thank Karl Staples, Clinical & Experimental Sciences, University of Southampton, UK, for his valuable support on cDNA microarray analysis. Furthermore, we thank Kerstin Skokann for excellent technical assistance.
The authors declare that they have no conflict of interest related to the publication of this manuscript.
- 6.Matsui H, Wagner VE, Hill DB, Schwab UE, Rogers TD, Button B, Taylor RM 2nd, Superfine R, Rubinstein M, Iglewski BH et al (2006) A physical linkage between cystic fibrosis airway surface dehydration and Pseudomonas aeruginosa biofilms. Proc Natl Acad Sci U S A 103:18131–18136PubMedCentralPubMedCrossRefGoogle Scholar
- 22.del Fresno C, Garcia-Rio F, Gomez-Pina V, Soares-Schanoski A, Fernandez-Ruiz I, Jurado T, Kajiji T, Shu C, Marin E, Gutierrez del Arroyo A et al (2009) Potent phagocytic activity with impaired antigen presentation identifying lipopolysaccharide-tolerant human monocytes: demonstration in isolated monocytes from cystic fibrosis patients. J Immunol 182:6494–6507PubMedCrossRefGoogle Scholar