title: Triggering of TLR-3, -4, NOD2, and DC-SIGN reduces viral replication and increases T-cell activation capacity of HIV-infected human dendritic cells.
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.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.|INSERM, U955, IMRB Equipe-16, Vaccine Research Institute-VRI, Creteil, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Cardinaud
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Urrutia
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.
authors.forename: Angeline
authors.initials: A
authors.lastname: Rouers
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.
authors.forename: Pierre-Grégoire
authors.initials: PG
authors.lastname: Coulon
authors.affiliation: INSERM, U955, IMRB Equipe-16, Vaccine Research Institute-VRI, Creteil, France.
authors.forename: Jérome
authors.initials: J
authors.lastname: Kervevan
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Richetta
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bet
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Maze
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Larsen
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.
authors.forename: Maria-Candela
authors.initials: MC
authors.lastname: Iglesias
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.
authors.forename: Victor
authors.initials: V
authors.lastname: Appay
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Graff-Dubois
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.
authors.forename: Arnaud
authors.identifier: 0000-0002-5052-1678
authors.initials: A
authors.lastname: Moris
mesh_terms: D000071478:APOBEC Deaminases; D017951:Antigen Presentation; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000069452:Pathogen-Associated Molecular Pattern Molecules; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000071478:APOBEC Deaminases; D015815:Cell Adhesion Molecules; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase; D037181:Lectins, C-Type; D053473:Nod2 Signaling Adaptor Protein; D000069452:Pathogen-Associated Molecular Pattern Molecules; D011956:Receptors, Cell Surface; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C429018:NOD2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; C502889:APOBEC3 proteins, human
keywords: APOBEC3; CTL; DC-SIGN; HIV-1; NOD; TLR