Mycobacterium abscessus complex is a group of rapidly growing mycobacteria, and an emerging cause of non-tuberculous mycobacterial lung disease in patients with cystic fibrosis and chronic lung diseases, such as bronchiectasis. M. abscessus complex is the most drug-resistant of the mycobacterial pathogens, resulting in limited therapeutic options and a high treatment failure rate. M. abscessus complex is comprised of three closely related subspecies: M. abscessus (sensu stricto), M. massiliense and M. bolletii. M. abscessus encodes a functional erythromycin ribosomal methylase gene, erm(41), which modifies the binding site for macrolide antibiotics, causing inducible macrolide resistance. However, this inducible macrolide resistance is not seen in M. massiliense, as the erm(41) gene of this subspecies is non-functional. Accordingly, treatment success rates with macrolide-based antibiotic treatment are much higher in patients with M. massiliense infections than in those infected with M. abscessus. Precise speciation of M. abscessus complex is important for predicting antibiotic susceptibilities and patient outcome.
The aims of the present study were to investigate the expression of Toll-like receptor (TLR)2 on the peripheral blood monocytes of patients with nontuberculous mycobacterial (NTM) lung disease and healthy controls, and to assess the responses of these monocytes to TLR2 agonists such as Mycobacterium avium and lipoteichoic acid (LTA).Reverse transcriptase-PCR was used to analyse TLR2 mRNA expression in peripheral blood monocytes from 17 NTM patients and 10 healthy controls. mRNA and protein secretion levels were also determined for the cytokines interleukin (IL)-12 p40 and tumour necrosis factor (TNF)-a.Expression of TLR2 mRNA by peripheral blood monocytes after stimulation with M. avium or LTA was lower in NTM patients than in healthy controls. IL-12 p40 and TNF-a mRNA and cytokine secretion levels were also lower in patients than in healthy controls. Treatment with anti-TLR antibody decreased M. avium-and LTA-induced IL-12 p40 and TNF-a production in healthy controls, but not in NTM patients.The present results suggest that the downregulation of Toll-like receptor 2 and the resulting decreased production of interleukin-12 p40 and tumour necrosis factor-a following Mycobacterium avium or lipoteichoic acid stimulation may contribute to host susceptibility to nontuberculous mycobacterial lung disease.
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