Abstract
BackgroundSarcoidosis 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.MethodsTotal 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.ResultsWe 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.ConclusionsOverall, 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.
Highlights
Sarcoidosis is a systemic T helper 1 (Th1) inflammatory disease [1,2], primarily affecting the lungs
The relative gene expression of several M1 and M2 associated markers was quantified in cultured total bronchoalveolar lavage (BAL) cells and sorted alveolar macrophages (AMs) from sarcoidosis patients, with or without Löfgren’s syndrome, and healthy subjects
The expression of selected Toll-like receptor (TLR) was measured in sorted AMs, and IL-17A was measured in sorted CD4+ T cells
Summary
Sarcoidosis is a systemic T helper 1 (Th1) inflammatory disease [1,2], primarily affecting the lungs. The hallmark of disease is non-caseating granulomas where macrophages are essential components These cells are very heterogeneous, characterized by plasticity and functional polarization, with, as here named, M1 and M2 types, at the extremes of a continuum. That is IFNg, TNF and microbial products (e.g. lipopolysaccharide (LPS)), elicit the M1 form This phenotype is characterized by high capacity to present antigens and high capacity to produce IL-12 (promoting Th1 responses) and IL-23 (promoting maturation and survival of IL-17 producing T cells), as well as microbicidal nitric oxide and reactive oxygen intermediates. 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
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