Innate Immunity

Team Publications

Year of 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 Learn more
Summary

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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Year of 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 Learn more
Summary

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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Year of 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 Learn more
Summary

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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