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Low Mannose Binding Lectin, but Not L-Ficolin, Is Associated With Spontaneous Clearance of Hepatitis C Virus After Infection.

ABSTRACT: Some individuals can spontaneously clear the hepatitis C virus (HCV) after infection, whereas others develop a chronic infection. The exact mechanism of this phenomenon is unknown. We aimed to evaluate the association of plasma levels of MBL, L-ficolin, and cytokines with outcome of HCV infections in two groups of patients who cleared HCV spontaneously (CHS), and who developed chronic HCV infections (CHC). Altogether, 86 patients and 183 healthy controls were included. Of 86 patients, 36 had CHS and 50 had CHC. Concentrations of plasma MBL and L-ficolin were measured in patients and controls. Twenty plasma cytokines and adhesion molecules, including GM-CSF, ICAM-1, IFN-?, IFN-?, IL-1?, IL-1?, IL-10, IL-12p70, IL-13, IL-17A, IL-4, IL-8, IP-10, MCP-1, IL-6, MIP-1?, MIP-1?, sE-Selectin, sP-Selectin, and TNF-?, were determined in all patients and randomly selected 45 controls. The level of MBL was significantly lower in subjects with CHS than in healthy controls (median: 293.10 vs. 482.64 ng/ml, p = 0.008), whereas the level of MBL was significantly higher in patients with CHC than in controls (median: 681.32 vs. 482.64 ng/ml, p = 0.001). No such differences in plasma L-ficolin were observed. Plasma levels of all cytokines and adhesion molecules, except ICAM-1, were significantly higher in patients than in controls. Moreover, patients with CHC had significantly higher levels of IFN-?, IFN-?, IL-1?, IL-10, IL-13, IL-4, IL-6, and TNF-? than those with CHS. These findings implicate that lower levels of plasma MBL, together with lower levels of above mentioned cytokines may play a part in virus clearance of HCV infection.

SUBMITTER: Zhang J

PROVIDER: S-EPMC7686574 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Low Mannose Binding Lectin, but Not L-Ficolin, Is Associated With Spontaneous Clearance of Hepatitis C Virus After Infection.

Zhang Jing J Chen Ning N Chen Zhiyun Z Liu Yali Y Zheng Kai K Qiu Yundong Y Zhang Nan N Zhu Junping J Yu Haibin H He Qiushui Q

Frontiers in immunology 20201111

Some individuals can spontaneously clear the hepatitis C virus (HCV) after infection, whereas others develop a chronic infection. The exact mechanism of this phenomenon is unknown. We aimed to evaluate the association of plasma levels of MBL, L-ficolin, and cytokines with outcome of HCV infections in two groups of patients who cleared HCV spontaneously (CHS), and who developed chronic HCV infections (CHC). Altogether, 86 patients and 183 healthy controls were included. Of 86 patients, 36 had CHS ...[more]

PMID: 33262767

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Project description:Mannose-binding lectin (MBL) is a key soluble pathogen recognition protein of the innate immune system that binds specific mannose-containing glycans on the surfaces of microbial agents and initiates complement activation via the lectin pathway. Prior studies showed that MBL-dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. Here, we investigated the antiviral activity of MBL in infection by dengue virus (DENV), a related flavivirus. Using a panel of naïve sera from mouse strains deficient in different complement components, we showed that inhibition of infection by insect cell- and mammalian cell-derived DENV was primarily dependent on the lectin pathway. Human MBL also bound to DENV and neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Experiments with human serum from naïve individuals with inherent variation in the levels of MBL in blood showed a direct correlation between the concentration of MBL and neutralization of DENV; samples with high levels of MBL in blood neutralized DENV more efficiently than those with lower levels. Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis. IMPORTANCE Dengue virus (DENV) is a mosquito-transmitted virus that causes a spectrum of clinical disease in humans ranging from subclinical infection to dengue hemorrhagic fever and dengue shock syndrome. Four serotypes of DENV exist, and severe illness is usually associated with secondary infection by a different serotype. Here, we show that mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation, neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Moreover, we observed a direct correlation with the concentration of MBL in human serum and neutralization of DENV infection. Our studies suggest that common genetic polymorphisms that result in disparate levels and function of MBL in humans may impact DENV infection, pathogenesis, and disease severity.

Dataset Information

Low Mannose Binding Lectin, but Not L-Ficolin, Is Associated With Spontaneous Clearance of Hepatitis C Virus After Infection.

Publications

Low Mannose Binding Lectin, but Not L-Ficolin, Is Associated With Spontaneous Clearance of Hepatitis C Virus After Infection.

Similar Datasets

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