CD14 Is Involved in the Interferon Response of Human Macrophages to Rubella Virus Infection

Schilling, Erik; Pfeiffer, Lukas; Hauschildt, Sunna; Koehl, Ulrike; Claus, Claudia

doi:10.3390/biomedicines10020266

Cited by 3 publications

(3 citation statements)

References 61 publications

(88 reference statements)

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“…The reduced surface expression of CD14 observed in CHIKV-infected C20 cells is likely to be associated with induction of apoptosis similar to previous studies on CHIKV in human monocytes and Rubella virus infection in human macrophages ( Her et al., 2010 ; Schilling et al., 2022 ). Although we found a small subset of CHIKV-infected C20 microglial cells showing upregulation of HLA-DR, a previous study on CHIKV-infected human monocytes reported no alteration in the expression of this molecule ( Her et al., 2010 ).…”

Section: Discussionsupporting

confidence: 85%

Chikungunya virus infection in human microglial C20 cells induces mitochondria-mediated apoptosis

Kumar,

Santhoshkumar,

Venkataswamy

2024

Front. Cell. Infect. Microbiol.

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IntroductionChikungunya virus (CHIKV) infection is associated with acute clinical manifestations and chronic joint inflammation. CHIKV has emerged as a significant causative agent of central nervous system (CNS) complications, including encephalitis and related sequelae. Microglial cells, crucial for immune responses and tissue repair in the CNS, play a vital role in the host response to viral infections, with their activation potentially leading to either protection or pathology. In this study, the infection biology of CHIKV in the C20 human microglial cell line was investigated.MethodsThe permissiveness of C20 cells to CHIKV infection was assessed, and viral replication kinetics were compared to Vero E6 cells. Cytopathic effects of CHIKV infection on C20 cells were examined, along with ultrastructural changes using transmission electron microscopy. Additionally, apoptosis induction, mitochondrial membrane potential, and alterations in cell surface marker expression were evaluated by flow cytometry.ResultsCHIKV infection demonstrated permissiveness in C20 cells, similar to Vero cells, resulting in robust viral replication and cytopathic effects. Ultrastructural analysis revealed viral replication, mature virion formation, and distinctive cytoplasmic and nuclear changes in infected C20 cells. CHIKV infection induced significant apoptosis in C20 cells, accompanied by mitochondrial membrane depolarization and altered expression of cell surface markers such as CD11c, CD14, and HLA-DR. Notably, decreased CD14 expression was observed in CHIKV-infected C20 cells.DiscussionThe study findings suggest that CHIKV infection induces apoptosis in C20 microglial cells via the mitochondrial pathway, with significant alterations in cell surface marker expression, particularly CD14 that is linked with apoptosis induction. These observations provide valuable insights into the role of human microglial cells in the host response to CHIKV infection and contribute to the knowledge on the neuropathogenesis of this virus.

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Section: Discussionsupporting

confidence: 85%

Chikungunya virus infection in human microglial C20 cells induces mitochondria-mediated apoptosis

Kumar,

Santhoshkumar,

Venkataswamy

2024

Front. Cell. Infect. Microbiol.

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“…Our group recently demonstrated that the influence of rubella virus (RuV) infection on the metabolism of human macrophages can in most parts be attributed to IFN β formed during RuV infection. Exogenous IFN β induced a loss of the glycolytic reserve in human macrophages as was noted for RuV [ 6 ]. Olson et al reported similar results through their observation on the contribution of IFN β to the reduction in the glycolytic reserve in murine bone marrow-derived macrophages during infection with Mycobacterium tuberculosis [ 7 ].…”

Section: Introductionmentioning

confidence: 89%

Interferon Signaling-Dependent Contribution of Glycolysis to Rubella Virus Infection

et al. 2022

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Interferons (IFNs) are an essential part of innate immunity and contribute to adaptive immune responses. Here, we employed a loss-of-function analysis with human A549 respiratory epithelial cells with a knockout (KO) of the type I IFN receptor (IFNAR KO), either solely or together with the receptor of type III IFN (IFNAR/IFNLR1 KO). The course of rubella virus (RuV) infection on the IFNAR KO A549 cells was comparable to the control A549. However, on the IFNAR/IFNLR1 KO A549 cells, both genome replication and the synthesis of viral proteins were significantly enhanced. The generation of IFN β during RuV infection was influenced by type III IFN signaling. In contrast to IFNAR KO A549, extracellular IFN β was not detected on IFNAR/IFNLR1 KO A549. The bioenergetic profile of RuV-infected IFNAR/IFNLR1 KO A549 cells generated by extracellular flux analysis revealed a significant increase in glycolysis, whereas mitochondrial respiration was comparable between all three cell types. Moreover, the application of the glucose analogue 2-deoxy-D-glucose (2-DG) significantly increased viral protein synthesis in control A549 cells, while no effect was noted on IFNAR/IFNLR KO A549. In conclusion, we identified a positive signaling circuit of type III IFN signaling on the generation of IFN β during RuV infection and an IFN signaling-dependent contribution of glycolysis to RuV infection. This study on epithelial A549 cells emphasizes the interaction between glycolysis and antiviral IFN signaling and notably, the antiviral activity of type III IFNs against RuV infection, especially in the absence of both type I and III IFN signaling, the RuV replication cycle was enhanced.

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“…It was found that infection of anti-inflammatory M2-macrophages with rubella virus was accompanied by a reduction in CD14 expression and the interferon β response [ 6 ].…”

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confidence: 99%

Macrophages in Health and Non-Infectious Disease 2.0

2022

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CD14 Is Involved in the Interferon Response of Human Macrophages to Rubella Virus Infection

Cited by 3 publications

References 61 publications

Chikungunya virus infection in human microglial C20 cells induces mitochondria-mediated apoptosis

Chikungunya virus infection in human microglial C20 cells induces mitochondria-mediated apoptosis

Interferon Signaling-Dependent Contribution of Glycolysis to Rubella Virus Infection

Macrophages in Health and Non-Infectious Disease 2.0

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