Dysfunction of peripheral blood dendritic cells from patients with chronic hepatitis B virus infection

Wang, Fusheng; Xing, Li-He; Liu, Mingxu; Zhu, Chuanbing; Liu, Huigang; Wang, Huifen; Lei, Zhou-Yun

doi:10.3748/wjg.v7.i4.537

Cited by 77 publications

(55 citation statements)

References 24 publications

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“…Infection of DCs by HBV is even more controversial than in HCV, and the described functional defects are minimal. [95][96][97] The delayed appearance of HBVspecific immune responses after primary infection seems to depend more on the kinetics of HBV replication (i.e., HBV persists for at least 5-8 weeks in the newly infected host without detectable signs of efficient replication), than on immune dysfunctions. The evidence that HBVspecific CD4 ϩ and CD8 ϩ T cells become detectable a short time after the exponential increase in HBV replication 27,28 suggests that the DC function is not affected by the virus at the early phases of self-limited HBV infection.…”

Section: Role Of the Dendritic Cells In Virus Controlmentioning

confidence: 99%

Kinetics of the immune response during HBV and HCV infection

2003

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The innate immune system has a role not only in protecting the host during the initial period of virus infection, but also in shaping the nature of the adaptive immune response. In this review, we follow the kinetics of the virologic and immunologic events occurring from the time of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We primarily discuss how the early events after infection might influence the development of the adaptive immune response in these 2 important viral infections and how new strategies for more efficient preventive and therapeutic vaccines can be derived from this knowledge. (HEPATOLOGY 2003; 38:4-13.)H epatitis B (HBV) and hepatitis C (HCV) viruses are the 2 major causes of chronic liver inflammation worldwide. 1,2 Despite distinct virologic features, both viruses are preferentially hepatotropic, not directly cytopathic, and elicit liver diseases that share several aspects of their natural history. HBV and HCV infections share also some important features of the adaptive immune response. Multispecific antiviral CD4 and CD8 responses with a T-helper type 1 profile of cytokine production are detectable in the blood of subjects with a self-limited infection. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] These responses are stronger than those found in patients with chronic infection. [17][18][19][20][21] Based on these observations, it has been proposed that the ability to mount an efficient cellular immune response is the main mechanism responsible for HBV and HCV control, whereas a defect in this response leads to chronicity. 2,22 However, the lack of suitable animal models to study the pathogenesis of HBV and HCV infections has so far hampered a definitive demonstration that associations between different infection outcomes and different vigor and breadth of T-cell responses have a causative effect. A recent report in HCV-infected chimpanzees, in which a clear association between T-cell response and virus clearance was not found, 23 added a further note of caution. Even so, it is difficult to argue against the importance of the cellular immune response in HBV and HCV control. In chimpanzees infected with HCV, expansion of a multispecific and sustained HCV-specific CD8 ϩ T-cell-mediated response was observed in 2 of 2 animals that cleared the virus, but not in the 4 animals that developed a chronic infection. 24 These results have been confirmed by recent reports showing that expansion of interferon ␥ (IFN-␥) ϩ , CD8 ϩ , and CD4 ϩ T cells precedes viral clearance in patients studied during the incubation phase of acute HCV infection in man 10 and in HCV-infected chimpanzees. 25 Similar findings have been reported in animal models of HBV infection 26 and in patients studied during the incubation phase of HBV infection, 27 in whom reduced early expansion of virusspecific T cells was associated with virus persistence. Moreover, the importance of virus-specific CD8 ϩ T cells in HBV control has been confirmed further by CD8 ϩ T-cell deletion experiments performed in HBV-i...

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Section: Role Of the Dendritic Cells In Virus Controlmentioning

confidence: 99%

Kinetics of the immune response during HBV and HCV infection

2003

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“…The underlying causes of chronic HBV infection are likely multifaceted and potentially include peripheral deletion/exhaustion, a weak CD4 T-cell response, reduced dendritic cell (DC) numbers and functions, an immunosuppressive microenvironment, inhibition of antigen processing or presentation, and escape mutations in T-and B-cell epitopes (15). Among these causes, defects in the HBV antigen-presenting function of DCs and the low expression of costimulatory factors on DCs are the major causes of HBV persistence (1,30).…”

Section: Introductionmentioning

confidence: 99%

α-Mannosidase I Protein Expression in Peripheral Blood Mononuclear Cells Is Upregulated During Hepatitis B Virus Infection

Jiang

Tian

et al. 2016

Viral Immunology

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Hepatitis B virus (HBV) has been reported to be recognized by dendritic cell-specific ICAM-3-grabbing nonintegrin in the presence of the a-mannosidase I inhibitor kifunensine, whereas native HBV is not. The aim of our study was to determine whether changes in a-mannosidase I expression in peripheral blood mononuclear cells (PBMCs) occur in patients with HBV infection. Peripheral blood was collected from 90 HBV-infected patients (grouped into immune tolerance, chronic hepatitis B, or inactive carrier group based on their clinical states) and 30 healthy donors. Expression of the three a-mannosidase I subtypes, MAN1A1, MAN1A2, and MAN1C1, was measured using western blot analyses. Compared with the healthy controls, significant increases in the MAN1A1, MAN1A2, and MAN1C1 expression levels were observed in the three HBV-infected groups, among whom the immune tolerance group showed the largest increase. For the patients in the immune tolerance phase, the expression levels of both MAN1A1 and MAN1A2 were linearly and positively correlated with the hepatitis B e antigen (HBeAg) titer and HBV DNA level, although a positive correlation was only found between MAN1C1 expression and the HBeAg titer. These results indicate that increased a-mannosidase I expression in PBMCs may play an important role in HBV immune escape and that its expression level is closely related to viral replication activity.

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“…In viral hepatitis, dysfunction of DCs from peripheral blood has been reported. In patients with chronic hepatitis B, maturation of DCs from peripheral blood of patients after incubation with cytokines is lower than that of normal subjects with lower expression of HLA-DR and costimulatory molecules in the former population (Wang et al, 2001), leading to low allostimulatory function of DCs from CHB patients. The mechanism of impairment of DC function in patients with chronic hepatitis B is unclear, but both HBV particles and purified HBsAg may have immunomodulatory capacity and may directly contribute to the dysfunction of myeloid DCs (Op den Brouw et al, 2009).…”

Section: Dysfunction Of Dcsmentioning

confidence: 99%