Low interleukin-10 production by monocytes of patients with a self-limiting hepatitis C virus infection |
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Authors: | G Martin-Blondel A Gales J Bernad L Cuzin P Delobel K Barange J Izopet B Pipy L Alric |
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Institution: | EA2405 UMR3 MD-UM-UPS, UniversitéPaul Sabatier Toulouse III, France;;Service de médecine interne, Fédération digestive du CHU Toulouse Purpan, France;;Service des maladies infectieuses et tropicales, CHU Toulouse Purpan, France;;INSERM, U563, Toulouse, France;;and Service d'hépatogastroentérologie, Fédération digestive du CHU Toulouse Purpan, France |
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Abstract: | Summary. Host factors seem to be crucial for the spontaneous clearance of hepatitis C virus (HCV). Monocytes play a pivotal role in innate immunity and help regulate adaptive responses. This study assesses the characteristics of monocytes from patients with self-limiting HCV infections. We studied 35 consecutive patients 11 with a self-limiting HCV infection, 16 chronically infected with HCV and sustained virological responders (SVR) following antiviral therapy, and eight chronically infected HCV but untreated] and eight healthy donors (HD). The production of interleukin (IL)-10, tumour necrosis factor-alpha (TNF-α) and IL-12p40 by monocytes stimulated with lipopolysaccharides(LPS) or HCV Core protein was measured by enzyme-linked immunoassay. Monocyte surface markers were analysed by flow cytometry. LPS and Core protein triggered IL-10 and TNF-α production, but monocytes from self-limiting infection patients produced significantly less IL-10 and TNF-α than those of SVR, chronically infected or HD ( P < 0.05), while IL-12p40 production was unchanged. This cytokine production profile did not appear to be due to expansion of the CD14+ CD16+ monocyte subset or to a classical or alternative activation monocyte profile. Monocytes from self-limiting infection patients had more CCR7 than those from SVR or chronically infected patients ( P < 0.05). Monocytes of self-limiting infection patients appear to produce little IL-10 and TNF-α in response to viral or unspecific stimulation and to have a higher CCR7 expression. This profile seems to be independent to a particular monocyte subset or activation state. Low IL-10 production may help establish an effective immune response and spontaneous HCV clearance. |
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Keywords: | cytokine hepatitis C virus innate immunity monocytes self-limiting infection |
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