HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway

Zhang, Qianqian; Wang, Yang; Zhai, Naicui; Song, Haiou; Li, Haijun; Yang, Yang; Li, Tianyang; Guo, Xingxing; Chi, Baorong; Niu, Junqi; Crispe, Ian Nicholas; Su, Lishan; Tu, Zhengkun

doi:10.1038/srep36160

Cited by 42 publications

(51 citation statements)

References 49 publications

(59 reference statements)

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“…Purified NK cells stimulated with IL‐18 and/or poly I:C were collected and lysed for Western blotting analysis as described previously . Briefly, cells were collected by centrifugation and resuspended in RIPA buffer (Cell Signalling Technology) to extract protein.…”

Section: Methodsmentioning

confidence: 99%

Activated NK cells kill hepatic stellate cells via p38/PI3K signaling in a TRAIL-involved degranulation manner

Yang

Song

et al. 2019

Journal of Leukocyte Biology

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NK cells are important in regulating hepatic fibrosis via their cytotoxic killing of hepatic stellate cells (HSCs). NK cells are activated by both cytokines such as IL‐12 and IL‐18, and innate immune stimuli such as ligation of TLRs. The secretion of IL‐18 depends upon activation of the inflammasome, whereas TLRs are stimulated by microbial products. In the case of NK cells, IL‐18 acts synergistically with stimulation of TLR3 to cause cell activation and cytotoxic function. In the present study, we activated NK cells to kill HSCs via IL‐18 and TLR3 ligand stimulation, and dissected the signaling pathways or molecules critical for such activation or killing. We find that such activation depends on signaling via the p38/PI3K/AKT pathway, and that the activated NK cells mediate HSC death in a TRAIL‐involved mechanism. As liver fibrosis is a major global health problem with no good solution, these results emphasize that the p38/PI3K/AKT pathway in NK cells may be a novel drug target to promote fibrosis regression.

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Section: Methodsmentioning

confidence: 99%

Activated NK cells kill hepatic stellate cells via p38/PI3K signaling in a TRAIL-involved degranulation manner

Yang

Song

et al. 2019

Journal of Leukocyte Biology

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“…To observe the effects of AFB 1 on the polarization of SIV-infected PAMs, PAMs were seeded on coverslips and infected with SIV for 24 h. Subsequently, groups of cells were further exposed to polarizing cytokines and AFB 1 for an additional 24 h, as follows: Group 1 (M1 control): LPS (100 ng/ml) plus IFN-γ (25 ng/ ml); Group 2 (M2 control): IL-4 (25 ng/ml) [30][31][32]; Group 3: AFB 1 (0 µg/ml); Group 4: AFB 1 (0.02 µg/ml); and Group 5: AFB 1 (0.04 µg/ml). At the end of the incubation period, PAMs were washed three times with PBS and were then fixed in 2.5% glutaraldehyde for 4 h at 4°C.…”

Section: Observation Of Pam Polarization By Scanning Electron Microscopymentioning

confidence: 99%

Low-Level Aflatoxin B1 Promotes Influenza Infection and Modulates a Switch in Macrophage Polarization from M1 to M2

Sun

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Swine influenza virus (SIV) is a major pathogen of both animals and humans. Afatoxin B1 (AFB₁) is one of the most common mycotoxins in feed and food. However, the central contribution of AFB₁ to SIV infection remains unclear. Methods: Here, TCID₅₀ assays, fluorescence-based quantitative real-time PCR, western blotting, immunofluorescence staining, histopathological examination, flow cytometry and scanning electron microscopy were performed to investigate the involvement and underlying mechanism of AFB₁ in SIV infection in vivo and in vitro using mouse models and porcine alveolar macrophage (PAM) models, respectively. Results: The in vivo study showed that low levels of AFB₁ promoted SIV infection and increased its severity, as demonstrated by the increased mRNA expression of viral matrix protein (M); by the increased protein expression of nucleoprotein (NP), matrix protein 1 and ion channel protein; and by animal weight loss, lung index and lung histologic damage. In addition, the increased occurrence of SIV infection accompanied by increases in the level of IL-10 in sera and lungs, in the spleen index and in the number of CD206-positive mouse alveolar macrophages but decreases in the level of TNF-α in sera and lungs, in the thymus index and in the number of CD80-positive mouse alveolar macrophages was observed in SIV-infected mice after low-level AFB₁ exposure. The in vitro study showed that low concentrations of AFB₁ promoted SIV infection, as demonstrated by the increases in viral titers and viral M mRNA and NP expression levels in SIV-infected PAMs as well as by the number of cells positive for NP protein expression. Furthermore, AFB₁ promoted the polarization of SIV-infected PAMs to the M1 phenotype at 8 hpi and to the M2 phenotype at 24 hpi, as measured by the increases in IL-10 expression and in the number of CD206-positive PAMs as well as by the morphological changes observed by scanning electron microscopy. The administration of the immune stimulant lipopolysaccharide (LPS) reversed the switch in PAM polarization from M2 to M1 and thereby counteracted the promotion of influenza virus infection induced by AFB₁. Conclusion: Our results are the first to confirm that low-level exposure to AFB₁ promotes SIV infection and modulates a switch in macrophage polarization from M1 to M2. The work reported here provides important data that point to a role for AFB₁ in SIV infection, and it opens a new field of study.

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“…One of the most important effector functions of macrophages is the capacity to phagocytose microbial pathogens [23]. Macrophages can recognize self-and non-self-particles and phagocytose them for destruction or antigen presentation.…”

Section: Phagocytosis Is Unaffected By the Presence Of Ebov Sgpmentioning

confidence: 99%

Ebola virus secreted glycoprotein decreases the anti-viral immunity of macrophages in early inflammatory responses

Bradley

Harrison

Corey

et al. 2018

Cellular Immunology

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During Ebola virus (EBOV) infection, secreted glycoprotein (sGP) is found in large quantities in the serum of both patients and infected animal models. It is thought to serve as a decoy for anti-EBOV antibodies. Using an in vitro model incorporating treatment of non-infected human THP-1 macrophages with recombinant EBOV sGP, this study sought to examine the impact of sGP upon key macrophage functions. Macrophage polarization and phagocytic capacity of activated macrophages were found to be unaltered by sGP treatment. However, treatment with sGP inhibited macrophage production of the pro-inflammatory cytokines TNFα and IL-6 while the yield of anti-inflammatory cytokine, IL-10, remained intact. Interestingly, the migratory ability of macrophages was also diminished by sGP, potentially due to a decrease in expression of CD11b, a vital macrophage integrin. Thus, EBOV sGP may operate to diminish functional contributions of non-infected macrophages to increase the potential viral dissemination.

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HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway

Cited by 42 publications

References 49 publications

Activated NK cells kill hepatic stellate cells via p38/PI3K signaling in a TRAIL-involved degranulation manner

Activated NK cells kill hepatic stellate cells via p38/PI3K signaling in a TRAIL-involved degranulation manner

Low-Level Aflatoxin B1 Promotes Influenza Infection and Modulates a Switch in Macrophage Polarization from M1 to M2

Ebola virus secreted glycoprotein decreases the anti-viral immunity of macrophages in early inflammatory responses

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