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Defective response to Toll‐like receptor 3 and 4 ligands by activated monocytes in chronic hepatitis C virus infection
Author(s) -
Villacres M. C.,
Literat O.,
DeGiacomo M.,
Du W.,
Frederick T.,
Kovacs A.
Publication year - 2008
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2007.00904.x
Subject(s) - immunology , tlr7 , tlr4 , toll like receptor , immune system , tlr3 , hepatitis c virus , tumor necrosis factor alpha , innate immune system , cytokine , biology , virus , medicine
Summary. Toll‐like receptors (TLR) have a critical role in innate immunity against pathogens. We investigated the cytokine response to TLR stimulation in peripheral blood cells of subjects infected with hepatitis C virus (HCV) and / or human immunodeficiency virus (HIV) in the Women Interagency HIV Study (WIHS) cohort. Interleukin (IL)‐6 in response to TLR3 and TLR4 ligands such as polyinosinic‐polycytidylic acid and lipopolysaccharide was significantly compromised in HCV‐infected women. High spontaneous secretion of IL‐6 suggested pre‐existing cell activation as a factor mediating reduced responses to TLR3 and TLR4 stimulation. To a lesser extent, tumour necrosis factor‐α and IL‐1β responses to TLR stimulation were also compromised. Monocytes, but not B cells or NK cells, were identified as the cell population spontaneously secreting cytokines and also as the cells responding to TLR stimulation. These results highlight a functional defect in antigen‐presenting cells of women with HCV infection or co‐infection. In women with existing HIV co‐infection, decreased cytokine function of antigen‐presenting cells suggests another mechanism contributing to immune dysfunction in addition to the HIV‐associated CD4 defect.