No evidence of altered alveolar macrophage polarization, but reduced expression of TLR2, in bronchoalveolar lavage cells in sarcoidosis.
BACKGROUND
Sarcoidosis is a granulomatous inflammatory disease, possibly of infectious aetiology. We aimed to investigate whether the degree of functional polarization of alveolar macrophages (AMs), or Toll-like receptor (TLR) expression, is associated with sarcoidosis or with distinct clinical manifestations of this disease.


METHODS
Total BAL cells (cultured four or 24 h in medium, or stimulated 24 h with LPS) from 14 patients and six healthy subjects, sorted AMs from 22 patients (Löfgren's syndrome n = 11) and 11 healthy subjects, and sorted CD4+ T cells from 26 patients (Löfgren's syndrome n = 13) and seven healthy subjects, were included. Using real-time PCR, the relative gene expression of IL-10, IL-12p35, IL-12p40, IL-23p19, CCR2, CCR7, iNOS, CXCL10, CXCL11, CXCL16, CCL18, CCL20, CD80, and CD86, and innate immune receptors TLR2, TLR4, and TLR9, was quantified in sorted AMs, and for selected genes in total BAL cells, while IL-17A was quantified in T cells.


RESULTS
We did not find evidence of a difference with regard to alveolar macrophage M1/M2 polarization between sarcoidosis patients and healthy controls. TLR2 gene expression was significantly lower in sorted AMs from patients, particular in Löfgren's patients. CCL18 gene expression in AMs was significantly higher in patients compared to controls. Additionally, the IL-17A expression was lower in Löfgren's patients' CD4+ T cells.


CONCLUSIONS
Overall, there was no evidence for alveolar macrophage polarization in sarcoidosis. However, there was a reduced TLR2 mRNA expression in patients with Löfgren's syndrome, which may be of relevance for macrophage interactions with a postulated sarcoidosis pathogen, and for the characteristics of the ensuing T cell response.
Wikén
Maria
M
Respiratory Medicine Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. maria.wiken@ki.se
Idali
Farah
F
Al Hayja
Muntasir Abo
MA
Grunewald
Johan
J
Eklund
Anders
A
Wahlström
Jan
J
D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017565:Sarcoidosis, Pulmonary / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2
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