Attenuation of toll-like receptor 2-mediated innate immune response in patients with alcoholic chronic liver disease


Adelino F. Leite Moreira, Al. Prof. Hernâni Monteiro; 4200-319, Porto – Portugal
Tel: +351 22 5513644
Fax: +351 22 5513646


Background: Alcoholic chronic liver disease (ACLD) is a common form of acquired immunodeficiency.

Aim: To evaluate ex vivo toll-like receptor (TLR) 2 and TLR4 innate immune response in stable ACLD.

Methods: Blood was collected from 26 males with stable ACLD and from 17 controls. Serum was used for lipopolysaccharide (LPS), sCD14, LPS-binding protein (LBP), tumour necrosis factor-alpha (TNF-α) and interleukin 10 (IL-10) quantification. Peripheral blood monocytes (PBM) protein expression of TLR2 and TLR4 was determined by flow cytometry. Primary cultures of anti-CD11b positive selected PBM were stimulated with the TLR2/TLR6 ligand zymosan (Zym), with TLR2/TLR1 ligand lipopeptide (Lp) and with TLR4 ligand LPS. PBM TLR1, TLR2, TLR4, TLR6, MD2, CD14, TNF-α and IL-10 gene expression was evaluated by reverse transcription-polymerase chain reaction.

Results: Stable ACLD patients showed increased circulating LPS (+22.5±4.1%), LBP (+60.6±12.2%) and sCD14 (+23.5±4.6%), with no differences in TNF-α and IL-10. Zym and Lp, but not LPS, induced TNF-α production by monocytes was blunted in ACLD (−66±20.4% Zym; −40.1±13.5% Lp; P<0.05). Basal TNF-α mRNA expression was decreased in PBM from ACLD patients (−50.1±21.0%; P<0.05), with no significant differences in the other studied genes. Results were similar in Child–Pugh A and B/C patients.

Conclusions: Patients with stable ACLD show an attenuation of TLR2-mediated innate immune response in PBM, which may represent an important mechanism for acquired immunodeficiency. This was neither related with decreased TLR2 or its co-receptors expression nor with impaired TLR4 activation, being already present in the early stages of disease.