Triggering of TLR-3, -4, NOD2, and DC-SIGN reduces viral replication and increases T-cell activation capacity of HIV-infected human dendritic cells

Sylvain Cardinaud; Alejandra Urrutia; Angeline Rouers; Pierre-Grégoire Coulon; Jérome Kervevan; Clémence Richetta; Anne Bet; Emmanuel A Maze; Martin Larsen; Maria-Candela Iglesias; Victor Appay; Stéphanie Graff-Dubois; Arnaud Moris

doi:10.1002/eji.201646603

Triggering of TLR-3, -4, NOD2, and DC-SIGN reduces viral replication and increases T-cell activation capacity of HIV-infected human dendritic cells

Eur J Immunol. 2017 May;47(5):818-829. doi: 10.1002/eji.201646603. Epub 2017 Apr 13.

Affiliations

¹ Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.
² INSERM, U955, IMRB Equipe-16, Vaccine Research Institute-VRI, Creteil, France.
³ Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.

PMID: 28266028
DOI: 10.1002/eji.201646603

Abstract

A variety of signals influence the capacity of dendritic cells (DCs) to mount potent antiviral cytotoxic T-cell (CTL) responses. In particular, innate immune sensing by pathogen recognition receptors, such as TLR and C-type lectines, influences DC biology and affects their susceptibility to HIV infection. Yet, whether the combined effects of PPRs triggering and HIV infection influence HIV-specific (HS) CTL responses remain enigmatic. Here, we dissect the impact of innate immune sensing by pathogen recognition receptors on DC maturation, HIV infection, and on the quality of HS CTL activation. Remarkably, ligand-driven triggering of TLR-3, -4, NOD2, and DC-SIGN, despite reducing viral replication, markedly increased the capacity of infected DCs to stimulate HS CTLs. This was exemplified by the diversity and the quantity of cytokines produced by HS CTLs primed by these DCs. Infecting DCs with viruses harboring members of the APOBEC family of antiviral factors enhanced the antigen-presenting skills of infected DCs. Our results highlight the tight interplay between innate and adaptive immunity and may help develop innovative immunotherapies against viral infections.

Keywords: APOBEC3; CTL; DC-SIGN; HIV-1; NOD; TLR.

MeSH terms

APOBEC Deaminases
Antigen Presentation
Cell Adhesion Molecules / genetics
Cell Adhesion Molecules / immunology
Cell Adhesion Molecules / metabolism
Cytidine Deaminase
Cytosine Deaminase / genetics
Cytosine Deaminase / metabolism
Dendritic Cells / immunology*
Dendritic Cells / physiology
Dendritic Cells / virology*
HIV-1 / immunology
HIV-1 / physiology*
Humans
Lectins, C-Type / genetics
Lectins, C-Type / immunology
Lectins, C-Type / metabolism
Lymphocyte Activation*
Nod2 Signaling Adaptor Protein / genetics
Nod2 Signaling Adaptor Protein / immunology
Nod2 Signaling Adaptor Protein / metabolism
Pathogen-Associated Molecular Pattern Molecules
Receptors, Cell Surface / genetics
Receptors, Cell Surface / immunology
Receptors, Cell Surface / metabolism
T-Lymphocytes, Cytotoxic / immunology
Toll-Like Receptor 3 / genetics
Toll-Like Receptor 3 / immunology
Toll-Like Receptor 3 / metabolism
Toll-Like Receptor 4 / genetics
Toll-Like Receptor 4 / immunology
Toll-Like Receptor 4 / metabolism
Virus Replication*

Substances

Cell Adhesion Molecules
DC-specific ICAM-3 grabbing nonintegrin
Lectins, C-Type
NOD2 protein, human
Nod2 Signaling Adaptor Protein
Pathogen-Associated Molecular Pattern Molecules
Receptors, Cell Surface
TLR3 protein, human
TLR4 protein, human
Toll-Like Receptor 3
Toll-Like Receptor 4
Cytosine Deaminase
APOBEC Deaminases
APOBEC3 proteins, human
Cytidine Deaminase