title: Dendritic cell stimulation by mycobacterial Hsp70 is mediated through CCR5.
abstract: An effective host immune response to mycobacterial infection must control pathogen dissemination without inducing immunopathology. Constitutive overexpression of mycobacterial heat shock protein (myHsp70) is associated with impaired bacterial persistence, but the immune-mediated mechanisms are unknown. We found that myHsp70, in addition to enhancing antigen delivery to human dendritic cells, signaled through the CCR5 chemokine receptor, promoting dendritic cell aggregation, immune synapse formation between dendritic cells and T cells, and the generation of effector immune responses. Thus, CCR5 acts as a pattern-recognition receptor for myHsp70, which may have implications for both the pathophysiology of tuberculosis and the use of myHsps in tumor-directed immunotherapy.
authors.affiliation: Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK.
authors.forename: R Andres
authors.initials: RA
authors.lastname: Floto
authors.forename: Paul A
authors.initials: PA
authors.lastname: MacAry
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Boname
authors.forename: Tan Suet
authors.initials: TS
authors.lastname: Mien
authors.forename: Beate
authors.initials: B
authors.lastname: Kampmann
authors.forename: James R
authors.initials: JR
authors.lastname: Hair
authors.forename: Oh Seen
authors.initials: OS
authors.lastname: Huey
authors.forename: Edith N G
authors.initials: EN
authors.lastname: Houben
authors.forename: Jean
authors.initials: J
authors.lastname: Pieters
authors.forename: Cheryl
authors.initials: C
authors.lastname: Day
authors.forename: Wulf
authors.initials: W
authors.lastname: Oehlmann
authors.forename: Mahavir
authors.initials: M
authors.lastname: Singh
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lehner
mesh_terms: D001426:Bacterial Proteins / Q000276:immunology / Q000502:physiology*; D020013:Calcium Signaling; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002449:Cell Aggregation; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000648:ultrastructure; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology* / Q000648:ultrastructure; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D009163:Mycobacterium bovis / Q000276:immunology / Q000502:physiology; D009169:Mycobacterium tuberculosis; D011554:Pseudopodia / Q000648:ultrastructure; D019713:Receptors, CCR5 / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D015815:Cell Adhesion Molecules; D018840:HSP70 Heat-Shock Proteins; C444642:HSP70 protein, Mycobacterium tuberculosis; D015850:Interleukin-6; D019713:Receptors, CCR5