Disordered Toll-like receptor 2 responses in the pathogenesis of pulmonary sarcoidosis.

Abstract:

:In this study, we hypothesized that the granulomatous disorder sarcoidosis is not caused by a single pathogen, but rather results from abnormal responses of Toll-like receptors (TLRs) to conserved bacterial elements. Unsorted bronchoalveolar lavage (BAL) cells from patients with suspected pulmonary sarcoidosis and healthy non-smoking control subjects were stimulated with representative ligands of TLR-2 (in both TLR-2/1 and TLR-2/6 heterodimers) and TLR-4. Responses were determined by assessing resulting production of tumour necrosis factor (TNF)-α and interleukin (IL)-6. BAL cells from patients in whom sarcoidosis was confirmed displayed increased cytokine responses to the TLR-2/1 ligand 19-kDa lipoprotein of Mycobacterium tuberculosis (LpqH) and decreased responses to the TLR-2/6 agonist fibroblast stimulating ligand-1 (FSL)-1. Subsequently, we evaluated the impact of TLR-2 gene deletion in a recently described murine model of T helper type 1 (Th1)-associated lung disease induced by heat-killed Propionibacterium acnes. As quantified by blinded scoring of lung pathology, P. acnes-induced granulomatous pulmonary inflammation was markedly attenuated in TLR-2(-/-) mice compared to wild-type C57BL/6 animals. The findings support a potential role for disordered TLR-2 responses in the pathogenesis of pulmonary sarcoidosis.

journal_name

Clin Exp Immunol

authors

Gabrilovich MI,Walrath J,van Lunteren J,Nethery D,Seifu M,Kern JA,Harding CV,Tuscano L,Lee H,Williams SD,Mackay W,Tomashefski JF Jr,Silver RF

doi

10.1111/cei.12138

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

512-22

issue

3

eissn

0009-9104

issn

1365-2249

journal_volume

173

pub_type

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