Immunité innée

Publications de l’équipe

Année de publication : 2013

Xavier Lahaye, Takeshi Satoh, Matteo Gentili, Silvia Cerboni, Cécile Conrad, Ilse Hurbain, Ahmed El Marjou, Christine Lacabaratz, Jean-Daniel Lelièvre, Nicolas Manel (2013 Sep 6)

The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells.

Immunity : 1132-42 : DOI : 10.1016/j.immuni.2013.11.002 En savoir plus
Résumé

HIV-2 is less pathogenic for humans than HIV-1 and might provide partial cross-protection from HIV-1-induced pathology. Although both viruses replicate in the T cells of infected patients, only HIV-2 replicates efficiently in dendritic cells (DCs) and activates innate immune pathways. How HIV is sensed in DC is unknown. Capsid-mutated HIV-2 revealed that sensing by the host requires viral cDNA synthesis, but not nuclear entry or genome integration. The HIV-1 capsid prevented viral cDNA sensing up to integration, allowing the virus to escape innate recognition. In contrast, DCs sensed capsid-mutated HIV-1 and enhanced stimulation of T cells in the absence of productive infection. Finally, we found that DC sensing of HIV-1 and HIV-2 required the DNA sensor cGAS. Thus, the HIV capsid is a determinant of innate sensing of the viral cDNA by cGAS in dendritic cells. This pathway might potentially be harnessed to develop effective vaccines against HIV-1.

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Takeshi Satoh, Nicolas Manel (2013 Jan 19)

Gene transduction in human monocyte-derived dendritic cells using lentiviral vectors.

Methods in molecular biology (Clifton, N.J.) : 401-9 : DOI : 10.1007/978-1-62703-218-6_30 En savoir plus
Résumé

Monocyte-derived dendritic cells (MDDCs) are widely used in the field of human immunology. Although a variety of gene delivery procedures have been used in MDDC, it has remained difficult to achieve robust gene transductions. In this chapter, we describe a procedure for high efficiency gene transduction in human MDDCs using lentiviral vectors. Gene transduction based on HIV-1-derived lentiviral vectors is restricted at the level of reverse transcription by the cellular protein SAMHD1 in MDDCs. Co-transduction of the MDDCs with helper particles derived from SIVmac that contain the viral protein Vpx removes this restriction, leading to a drastic increase in the rate of gene transduction. This procedure leads to nontoxic, efficient and stable transduction in MDDCs. It can be applied to any HIV-1-derived lentiviral vector, including shRNA lentiviral vectors for RNAi. Transduced MDDCs are not activated by the transduction and can be activated normally by TLR ligands.

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Année de publication : 2012

Aymeric Silvin, Nicolas Manel (2012 Sep 15)

Interactions between HIV-1 and innate immunity in dendritic cells.

Advances in experimental medicine and biology : 183-200 : DOI : 10.1007/978-1-4614-4433-6_7 En savoir plus
Résumé

Dendritic cells couple pathogen sensing with induction of innate and adaptive immune responses. Pathogen sensing in dendritic cells relies on interactions between molecular patterns of the pathogens and germline-encoded, also referred to as innate, receptors. In this chapter, we analyze some of the interactions between HIV-1 and the innate immune system in dendritic cells. The HIV-1 replication cycle is constituted by an extracellular and an intracellular phase. The two phases of the cycle provide distinct opportunities for interactions with cell-extrinsic and cell-intrinsic mechanisms in dendritic cells. According to the types of dendritic cells, the mechanisms of innate interactions between dendritic cells and HIV-1 lead to specific responses. These innate interactions may contribute to influencing and shaping the adaptive immune response against the virus.

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Année de publication : 2011

Nicolas Manel, Dan R Littman (2011 Jul 14)

Hiding in plain sight: how HIV evades innate immune responses.

Cell : 271-4 : DOI : 10.1016/j.cell.2011.09.010 En savoir plus
Résumé

Two groups have identified SAMHD1, a protein encoded by an Aicardi-Goutières Syndrome susceptibility gene, as the factor that restricts infection of macrophages and dendritic cells with HIV-1. Here we discuss implications of this discovery for induction of antiviral protective immunity.

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Année de publication : 2010

Nicolas Manel, Brandon Hogstad, Yaming Wang, David E Levy, Derya Unutmaz, Dan R Littman (2010 May 27)

A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells.

Nature : 214-7 : DOI : 10.1038/nature09337 En savoir plus
Résumé

Dendritic cells serve a key function in host defence, linking innate detection of microbes to activation of pathogen-specific adaptive immune responses. Whether there is cell-intrinsic recognition of human immunodeficiency virus (HIV) by host innate pattern-recognition receptors and subsequent coupling to antiviral T-cell responses is not yet known. Dendritic cells are largely resistant to infection with HIV-1, but facilitate infection of co-cultured T-helper cells through a process of trans-enhancement. Here we show that, when dendritic cell resistance to infection is circumvented, HIV-1 induces dendritic cell maturation, an antiviral type I interferon response and activation of T cells. This innate response is dependent on the interaction of newly synthesized HIV-1 capsid with cellular cyclophilin A (CYPA) and the subsequent activation of the transcription factor IRF3. Because the peptidylprolyl isomerase CYPA also interacts with HIV-1 capsid to promote infectivity, our results indicate that capsid conformation has evolved under opposing selective pressures for infectivity versus furtiveness. Thus, a cell-intrinsic sensor for HIV-1 exists in dendritic cells and mediates an antiviral immune response, but it is not typically engaged owing to the absence of dendritic cell infection. The virulence of HIV-1 may be related to evasion of this response, the manipulation of which may be necessary to generate an effective HIV-1 vaccine.

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