Amiloride Enhances Antigen Specific CTL by Faciliting HBV DNA Vaccine Entry into Cells

Geng, Shuang; Zhong, Yiwei; Wang, Shuang; Liu, Hu; Zou, Qiang; Xie, Xiaoping; Li, Chaofan; Yu, Qingling; He, Zhonghuai; Wang, Bin

doi:10.1371/journal.pone.0033015

Cited by 14 publications

(7 citation statements)

References 48 publications

(51 reference statements)

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“…CD11c ϩ DCs were isolated from spleen with CD11c MicroBeads, according to the manufacturer's instructions (Miltenyi Biotech, Cologne, Germany). The efficiency of isolation was assessed by flow cytometry assay, as previously described (35).…”

Section: Methodsmentioning

confidence: 99%

Herpes Simplex Virus 1 Suppresses the Function of Lung Dendritic Cells via Caveolin-1

Geng

et al. 2015

Clin Vaccine Immunol

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Caveolin-1 (Cav-1), the principal structural protein of caveolae, has been implicated as a regulator of virus-host interactions. Several viruses exploit caveolae to facilitate viral infections. However, the roles of Cav-1 in herpes simplex virus 1 (HSV-1) infection have not fully been elucidated. Here, we report that Cav-1 downregulates the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) in dendritic cells (DCs) during HSV-1 infection. As a result, Cav-1 deficiency led to an accelerated elimination of virus and less lung pathological change following HSV-1 infection. This protection was dependent on iNOS and NO production in DCs. Adoptive transfer of DCs with Cav-1 knockdown was sufficient to confer the protection to wild-type (WT) mice. In addition, Cav-1 knockout (KO) (Cav-1 ؊/؊ ) mice treated with an iNOS inhibitor exhibited significantly reduced survival compared to that of the nontreated controls. We found that Cav-1 colocalized with iNOS and HSV-1 in caveolae in HSV-1-infected DCs, suggesting their interaction. Taken together, our results identified Cav-1 as a novel regulator utilized by HSV-1 to evade the host antiviral response mediated by NO production. Therefore, Cav-1 might be a valuable target for therapeutic approaches against herpesvirus infections. Herpes simplex virus 1 (HSV-1) is a double-stranded DNA (dsDNA) virus belonging to the Alphaherpesvirus family, which causes oral herpes, encephalitis, keratitis, neonatal herpes, and pneumonia disease, establishing latency in the neurons after acute infection of mucosal tissues (1-3). Notably, HSV-1 can be isolated from the respiratory tract of immunosuppressed patients and newborn infants, where it induces pneumonitis, resulting in remarkable morbidity and mortality (4). Recent studies have suggested that HSV-1-induced bronchopneumonitis is common in nonimmunocompromised persons who are undergoing continuous mechanical ventilation (5). Currently, the mechanisms of HSV-1-induced pneumonia and obstructive pulmonary disease are not fully understood, although intranasal (i.n.) infection with HSV-1 in mice can be used as a model to investigate these mechanisms (4, 6, 7). Such investigations might reveal a valuable therapeutic approach for HSV-1-induced pneumonia.Innate defense cells and inflammatory factors serve as the firstline of host defense against viral infections. DCs can be recruited to the lungs and in the cornea of the eye, where they contribute to host defense (8, 9). Studies have shown that diphtheria toxin (DT)-induced depletion of DCs in CD11c-DTR mice (in which the DT receptor [DTR] is expressed under the control of the CD11c promoter) inhibited the migration of natural killer cells and neutrophils to locally infected cornea, resulting in severe pathology (10, 11). Moreover, involvement of the free radical nitric oxide (NO) has been indicated. This is a powerful vasodilator factor and cell signaling molecule, with a short half-life of 3 to ϳ4 s in the blood, and it is synthesized by nitric oxide s...

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Section: Methodsmentioning

confidence: 99%

Herpes Simplex Virus 1 Suppresses the Function of Lung Dendritic Cells via Caveolin-1

Geng

et al. 2015

Clin Vaccine Immunol

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“…Activation of antigen-specific T cell response is critical for the treatment of cancer and viral diseases [18][19][20][21]. The activated antigen specific effector T cells could migrate into inflammation or tumor deposits through lymph node [22].…”

Section: Regulation Of T Cell Activation By Dubsmentioning

confidence: 99%

Deubiquitinase as Potential Targets for Cancer Immunotherapy

2019

Journal of Cellular Immunology

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“…Clearance of hepatitis B virus (HBV) mainly depends on fully functional cytotoxic T lymphocytes (CTLs) (7,14). However, due to suppression of CTLs, HBV cannot be effectively and completely eliminated, leading to chronic infection with persistent replication of HBV and intermittent liver injury.…”

Section: Introductionmentioning

confidence: 99%

Expression of PD-L1 on CD4+CD25+Foxp3+ Regulatory T Cells of Patients with Chronic HBV Infection and Its Correlation with Clinical Parameters

et al. 2015

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Regulatory T cells (Tregs) play a pivotal role in suppressing specific antiviral immune responses during the progression of chronic hepatitis B virus infection (CHB) as well as tumorigenesis. Programmed death-1 ligand-1 (PD-L1) expressed on Tregs can transduce an inhibitory signal into effector T cells through interacting with programmed death-1 (PD-1). However, in CHB patients, the clinical significance of PD-L1 expression on Tregs has not been clearly described. This study investigated the frequency of circulating Tregs and PD-L1 expression on Tregs and analyzed their correlations with clinical parameters. The data show that both the frequency of CD4+CD25+FoxP3+ Tregs and PD-L1 expression on Tregs in the peripheral blood increased significantly in CHB patients when compared with healthy controls. At the same time, it is shown that PD-L1 expression on Tregs was positively correlated with the percentage of Tregs in CHB patients. Moreover, the results demonstrated that both Treg frequency and PD-L1 expression on Tregs positively correlated with the levels of alanine aminotransaminase (ALT) and aspartate aminotransferase (AST), both of which are indicators of the extent of liver injury. Taken together, these findings suggest that PD-L1 on Tregs might contribute to progression of hepatitis B virus infection through mediating the inhibitory function of Tregs. Thereby, blockade of interaction between Treg-expressing PD-L1 and PD-1 on effector T cells may be adopted as a potential therapeutic approach in CHB.

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Amiloride Enhances Antigen Specific CTL by Faciliting HBV DNA Vaccine Entry into Cells

Cited by 14 publications

References 48 publications

Herpes Simplex Virus 1 Suppresses the Function of Lung Dendritic Cells via Caveolin-1

Herpes Simplex Virus 1 Suppresses the Function of Lung Dendritic Cells via Caveolin-1

Deubiquitinase as Potential Targets for Cancer Immunotherapy

Expression of PD-L1 on CD4+CD25+Foxp3+ Regulatory T Cells of Patients with Chronic HBV Infection and Its Correlation with Clinical Parameters

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