Antiviral factors and type I/III interferon expression associated with regulatory factors in the oral epithelial cells from HIV-1-serodiscordant couples

Cervantes, Cesar A. C.; Oliveira, Luanda Mara da Silva; Manfrere, Kelly Cristina Gomes; Lima, Jozely Francisca Mello; Pereira, Newton Lindolfo; Duarte, Alberto J. S.; Sato, Maria Notomi

doi:10.1038/srep25875

Cited by 8 publications

(9 citation statements)

References 43 publications

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“…Among the different immunological factors thus far correlated with the HESN phenotype, Type-I Interferons seem to play a crucial role in controlling HIV-1 infection [3,4,[16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Sterol metabolism modulates susceptibility to HIV-1 Infection

Saulle

Ibba²,

Vittori³

et al. 2020

Aids

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Background 25-hydroxylase (CH25H) is an Interferon stimulated gene (ISG), which catalyzes the synthesis of 25-Hydroxycholesterol (25HC). 25HC intervenes in metabolic and infectious processes as controls cholesterol homeostasis and influences viral entry into host cells. We verified whether natural resistance to HIV-1 infection in HIV-1-exposed seronegative (HESN) individuals is at least partially mediated by particularities in sterol biosynthesis. Methods Peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages (MDMs) isolated from 15 sexually-exposed HESN and 15 healthy controls (HC) were in vitro HIV-1infected and analyzed for: 1) percentage of IFN-producing plasmacytoid Dendritic Cells (pDCs); 2) Cholesterol signaling and inflammatory response RNA expression; 3) resistance to HIV-1 infection. MDMs from 5 HC were in vitro HIV-1-infected in the absence/presence of exogenously added 25HC. Results IFN-producing pDCs were augmented in HESN compared to HCs both in unstimulated and in in vitro HIV-1-infected PBMCs (p<0.001). An increased expression of CH25H and of a number of genes involved in cholesterol metabolism (ABCA1, ABCG1, CYP7B1, LXR, OSBP, PPARSCARB1) was observed as well; this, was associated with a reduced susceptibility to in vitro HIV-1-infection of PBMCs and MDMs (p<0.01). Notably, addition of 25HC to MDMs resulted in increased cholesterol efflux and augmented resistance to in vitro HIV-1-infection. Conclusions Results herein show that in HESN sterol metabolism might be particularly efficient. This could be related to the activation of the IFN pathway and results into a reduced susceptibility to in vitro HIV-1 infection. These results suggest a possible basis for therapeutic interventions to modulate HIV-1 infection.

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“…Among the different immunological factors thus far correlated with the HESN phenotype, Type-I Interferons seem to play a crucial role in controlling HIV-1 infection [3,4,[16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Sterol metabolism modulates susceptibility to HIV-1 Infection

Saulle

Ibba²,

Vittori³

et al. 2020

Aids

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“…In addition, a polymorphism in the TLR9 gene is associated with HIV-1 infection, progression, and vertical transmission (21,(34)(35)(36). Importantly, the activation of innate immunity through increased TLR9 expression was found in oral epithelial cells from HESN individuals (25). Furthermore, our previous study (22) on drug-abused individuals also shows that decreased TLR9 expression and activity caused by drug abuse, accompanied by the decrease of key factors and cytokines (IRF7, IFN-α/β, etc.)…”

Section: Discussionmentioning

confidence: 66%

“…The mechanisms involved in mediating natural resistance to HIV-1 infection are multifactorial. The combined contributions of innate and adaptive immunity, as well as genetic factors, provide important advantages that allow a low susceptibility to infection (21,(23)(24)(25). Recently, several studies have examined the relationships between host innate immunity and HIV resistance in HESN individuals.…”

Section: Discussionmentioning

confidence: 99%

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Enhanced Signaling Through the TLR9 Pathway Is Associated With Resistance to HIV-1 Infection in Chinese HIV-1–Exposed Seronegative Individuals

Jiang

et al. 2020

Front. Immunol.

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Innate immunity is the first line of defense against invading pathogens and may mediate HIV-1 resistance in HIV-1-exposed seronegative (HESN) individuals. This study aims to identify components of innate immunity that confer natural HIV-1 resistance in Chinese HESN individuals. Specifically, we compared the expression levels of Toll-like receptors (TLRs) and associated pathway molecules in peripheral blood mononuclear cells (PBMCs), monocytes/macrophages, and plasma obtained from HESN and control individuals. HESN individuals had higher expression of TLR9, IRF7, IFN-α/β, RANTES, and MIP-1α/1β in PBMCs and plasma than control subjects. Upon TLR9 stimulation, significantly higher expression of TLR9 and IRF7, as well as higher production of IFN-α/β, RANTES, and MIP-1α/1β, was observed in PBMCs and monocytes/macrophages from HESN individuals than in the corresponding cells from control individuals. More importantly, both with and without TLR9 stimulation, the levels of HIV-1 replication in monocyte-derived macrophages (MDMs) from HESN individuals were significantly lower than those in MDMs from control individuals. These data suggest that increased TLR9 activity and subsequent release of antiviral factors contribute to protection against HIV-1 in HESN individuals.

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“…Much of the previous work of oral epithelial cell innate immunity has revolved around antibacterial aspects (McClure & Massari, 2014;Shnawa, 2016;Sugawara, Uehara, Tamai, & Takada, 2002), with the majority of IFN research involving the ability of OEC-produced IFN-γ, a type II IFN, to prime other OECs to secrete cytokines necessary for T cell and macrophage activation in the clearance of pathogenic, dysbiotic bacterial infections in the oral cavity (Mutlu, Scully, & Prime, 1991;Suga et al, 2013;Yumoto et al, 2001). While IFN-α and IFN-β have been shown to be secreted by OECs previously (Cervantes et al, 2016;Teixeira, Zhao, Kinane, & Benakanakere, 2019), our results demonstrate the ability of OECs to express not only IFNB and F I G U R E 1 Type I interferon expression in oral epithelial cells upon pattern recognition receptor stimulation. OKF6/Tert-1 cells were treated with 1 μg/ml poly(I:C) for up to 6 hr and measured for changes in type I interferon expression by RT-qPCR.…”

Section: Discussionmentioning

confidence: 99%

Type I interferon and interferon‐stimulated gene expression in oral epithelial cells

Brice

Figgins

et al. 2019

Molecular Oral Microbiology

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Oral epithelial cells (OEC) represent the first site of host interaction with viruses that infect the body through the oral route; however, their innate antiviral defense mechanisms yet to be defined. Previous studies have determined that OEC express pathogen‐, damage‐, or danger‐associated molecular patterns (PAMPs or DAMPs), but their expression of key antiviral innate immune mediators, including type I interferons (type I IFN) and interferon‐stimulated genes (ISGs) has not been studied extensively. We used the oral keratinocyte cell line, OKF6/TERT1, in the presence and absence of the viral mimics poly(I:C) and unmethylated CpG DNA, to define the expression of type I IFN and ISGs. We identified the basal expression of novel type I IFN genes IFNE and IFNK, while IFNB1 was induced by viral mimics, through the nuclear translocation of IRF3. Numerous ISGs were expressed at basal levels in OEC, with an apparent correlation between high expression and antiviral activity at the earlier stages of viral infection. Stimulation of OECs with poly(I:C) led to selective induction of ISGs, including MX1, BST2, PML, RSAD2, ISG15, and ZC3HAV1. Together, our results demonstrate that OECs exhibit a robust innate antiviral immune defense profile, which is primed to address a wide variety of pathogenic viruses that are transmitted orally.

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Antiviral factors and type I/III interferon expression associated with regulatory factors in the oral epithelial cells from HIV-1-serodiscordant couples

Cited by 8 publications

References 43 publications

Sterol metabolism modulates susceptibility to HIV-1 Infection

Sterol metabolism modulates susceptibility to HIV-1 Infection

Enhanced Signaling Through the TLR9 Pathway Is Associated With Resistance to HIV-1 Infection in Chinese HIV-1–Exposed Seronegative Individuals

Type I interferon and interferon‐stimulated gene expression in oral epithelial cells

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