Leukocyte immunoglobulin-like receptors maintain unique antigen-presenting properties of circulating myeloid dendritic cells in HIV-1-infected elite controllers.
Elite controllers maintain undetectable levels of HIV-1 replication in the absence of antiretroviral therapy, but the correlates of immune protection in this patient population are ill defined. Here, we demonstrate that in comparison to patients with progressive HIV-1 infection or healthy persons not infected with HIV-1, elite controllers have circulating myeloid dendritic cells with significantly increased antigen-presenting properties, while their ability to secrete proinflammatory cytokines is substantially diminished. This unique functional profile is associated with a distinct surface expression pattern of immunomodulatory leukocyte-immunoglobulin-like receptors (LILR) and a strong and selective upregulation of LILRB1 and LILRB3. Blockade of these two receptors by monoclonal antibodies or short interfering RNA (siRNA) abrogated the specific antigen-presenting properties of dendritic cells, implying an important regulatory role of these molecules. These data reveal previously unrecognized innate components of immune protection against HIV-1 in elite controllers and offer novel perspectives for the manipulation of host immunity for the prevention and treatment of HIV-1 infection.
Huang
Jinghe
J
Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, 149 13th Street, Room 5219, Boston, MA 02129, USA.
Burke
Patrick S
PS
Cung
Thai Duong Hong
TD
Pereyra
Florencia
F
Toth
Ildiko
I
Walker
Bruce D
BD
Borges
Luis
L
Lichterfeld
Mathias
M
Yu
Xu G
XG
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D020868:Gene Silencing; D015658:HIV Infections / Q000276:immunology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; C105299:LILRB1 protein, human; C527699:LILRB3 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic