Technical Advance: Measurement of iNKT cell responses at the single-cell level against rare HIV-1-infected dendritic cells in a mixed culture

Andersson, S; Paquin‐Proulx, Dominic; Kroll, Mirko; Sandberg, Johan K.; Moll, Markus

doi:10.1189/jlb.1012489

Cited by 3 publications

(6 citation statements)

References 28 publications

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“…Retinoic acid-treated DC express more CD1d molecules and display augmented ability to induce iNKT cell IFN-␥ responses (42). HIV-infected DC downregulate CD1d expression and fail to activate IFN-␥ production by iNKT cells (43). These data strongly suggest that CD1d expression levels are coupled to the activation status of NKT cells.…”

Section: Mansoni-infected Il-4r␣mentioning

confidence: 48%

“…CD1d expression by leukocytes is often altered following host exposure to bacteria and viruses, indicating that modulation of CD1d expression may be one strategy of the host immune response to infections (42,43). Retinoic acid-treated DC express more CD1d molecules and display augmented ability to induce iNKT cell IFN-␥ responses (42).…”

Section: Mansoni-infected Il-4r␣mentioning

confidence: 99%

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Helminth-Induced Interleukin-4 Abrogates Invariant Natural Killer T Cell Activation-Associated Clearance of Bacterial Infection

Hsieh

2014

Infect Immun

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Section: Mansoni-infected Il-4r␣mentioning

confidence: 48%

Section: Mansoni-infected Il-4r␣mentioning

confidence: 99%

Helminth-Induced Interleukin-4 Abrogates Invariant Natural Killer T Cell Activation-Associated Clearance of Bacterial Infection

Hsieh

2014

Infect Immun

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“…4A). We previously showed that this assay allows assessment of the iNKT cell response to the exogenous model antigen α-galactosylceramide (αGalCer) (38). The iNKT cell IFNγ production in response to mdDCs infected with wt HIV-1 was significantly reduced compared with uninfected mdDCs (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To generate DHIV3 Δ nef Δ vpu virus, the defective vpu gene was cloned into the DHIV3 Δ nef construct. The eGFP gene was cloned into the DHIV3 wt plasmid as previously described (38). DHIV3 is a replication-deficient HIV-1 construct based on the NL4-3 sequence carrying a deletion in the env gene and therefore requires VSV-G pseudotyping of the viruses to ensure infectivity.…”

Section: Methodsmentioning

confidence: 99%

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Innate Invariant NKT Cell Recognition of HIV-1–Infected Dendritic Cells Is an Early Detection Mechanism Targeted by Viral Immune Evasion

Paquin‐Proulx

Gibbs

Bächle

et al. 2016

The Journal of Immunology

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Invariant natural killer T (iNKT) cells are innate-like T cells that respond rapidly with a broad range of effector functions upon recognition of glycolipid antigens presented by CD1d. HIV-1 carries Nef- and Vpu-dependent mechanisms to interfere with CD1d surface expression, indirectly suggesting a role for iNKT cells in control of HIV-1 infection. Here, we investigated if iNKT cells can participate in the innate cell-mediated immune response to HIV-1. Infection of dendritic cells (DCs) with Nef- and Vpu-deficient HIV-1 induced upregulation of CD1d in a TLR7-dependent manner. Infection of DCs caused modulation of enzymes in the sphingolipid pathway and enhanced expression of the endogenous glucocylceramide antigen. Importantly, iNKT cells responded specifically to rare DCs productively infected with Nef- and Vpu-defective HIV-1. Transmitted founder viral isolates differed in their CD1d down-regulation capacity, suggesting that diverse strains may be differentially successful in inhibiting this pathway. Furthermore, both iNKT cells and DCs expressing CD1d and HIV-receptors resided in the female genital mucosa, a site where HIV-1 transmission occurs. Together, these findings suggest that innate iNKT cell sensing of HIV-1 infection in DCs is an early immune detection mechanism, which is independent of priming and adaptive recognition of viral antigen, and is actively targeted by Nef- and Vpu-dependent viral immune evasion mechanisms.

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Involvement of a C-terminal motif in the interference of primate lentiviral Vpu proteins with CD1d-mediated antigen presentation

Bächle

Sauter

Sibitz

et al. 2015

Sci Rep

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The HIV-1 accessory protein Vpu is emerging as a critical factor for viral evasion from innate immunity. We have previously shown that the Vpu proteins of two HIV-1 group M subtype B strains (NL4-3 and BaL) down-regulate CD1d from the surface of infected dendritic cells (DCs) and inhibit their crosstalk with the innate invariant natural killer T (iNKT) cells. In the present study, we have investigated the ability of a comprehensive set of primate lentiviral Vpu proteins to interfere with CD1d-mediated immunity. We found that CD1d down-regulation is a conserved function of Vpu proteins from HIV-1 groups M, O and P as well as their direct precursors SIVcpzPtt and SIVgor. At the group M subtype level, subtype C Vpu proteins were significantly weaker CD1d antagonists than subtype B Vpu proteins. Functional characterization of different mutants and chimeras derived from active subtype B and inactive subtype C Vpu proteins revealed that residues in the cytoplasmic domain are important for CD1d down-regulation. Specifically, we identified a C-terminal APW motif characteristic for group M subtype B Vpu proteins necessary for interference with CD1d surface expression. These findings support the notion that Vpu plays an important role in lentiviral evasion from innate immunity.

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Technical Advance: Measurement of iNKT cell responses at the single-cell level against rare HIV-1-infected dendritic cells in a mixed culture

Abstract: A microscopy-based assay to measure iNKT cell responses against rare HIV-1 infected dendritic cells, infected with an eGFP expressing reporter virus.

Cited by 3 publications

References 28 publications

Helminth-Induced Interleukin-4 Abrogates Invariant Natural Killer T Cell Activation-Associated Clearance of Bacterial Infection

Helminth-Induced Interleukin-4 Abrogates Invariant Natural Killer T Cell Activation-Associated Clearance of Bacterial Infection

Innate Invariant NKT Cell Recognition of HIV-1–Infected Dendritic Cells Is an Early Detection Mechanism Targeted by Viral Immune Evasion

Involvement of a C-terminal motif in the interference of primate lentiviral Vpu proteins with CD1d-mediated antigen presentation

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