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Sci Immunol. 2017 Jul 7;2(13). pii: eaai8071. doi: 10.1126/sciimmunol.aai8071.

Constitutive resistance to viral infection in human CD141+ dendritic cells.

Author information

1
Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.
2
Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
3
The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
4
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
5
Centre d'Immunologie de Marseille-Luminy, Aix Marseille University, UM2, INSERM U1104, CNRS UMR7280, France.
6
Institut Curie, PSL Research University, CNRS, UMR144, Molecular Mechanisms of Intracellular Transport, 75005 Paris, France.
7
Centre d'Immunologie et des Maladies Infectieuses-Paris, Pierre and Marie Curie University UMRS C7, INSERM U1135, CNRS ERL 8255, Paris, France.
8
INSERM U955, IMRB Equipe-16, Vaccine Research Institute (VRI), F-94010, Creteil, France.
9
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine; and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
10
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
11
Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
12
Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
13
Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
14
Precision Immunology Institute, Human Immune Monitoring Center, Tisch Cancer institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
15
Baylor Institute for Immunology Research, Dallas, TX 75204, USA. karolina.palucka@jax.org nicolas.manel@curie.fr.
16
Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France. karolina.palucka@jax.org nicolas.manel@curie.fr.

Abstract

Dendritic cells (DCs) are critical for the launching of protective T cell immunity in response to viral infection. Viruses can directly infect DCs, thereby compromising their viability and suppressing their ability to activate immune responses. How DC function is maintained in light of this paradox is not understood. By analyzing the susceptibility of primary human DC subsets to viral infections, we report that CD141+ DCs have an innate resistance to infection by a broad range of enveloped viruses, including HIV and influenza virus. In contrast, CD1c+ DCs are susceptible to infection, which enables viral antigen production but impairs their immune functions and survival. The ability of CD141+ DCs to resist infection is conferred by RAB15, a vesicle-trafficking protein constitutively expressed in this DC subset. We show that CD141+ DCs rely on viral antigens produced in bystander cells to launch cross-presentation-driven T cell responses. By dissociating viral infection from antigen presentation, this mechanism protects the functional capacity of DCs to launch adaptive immunity against viral infection.

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