Dendritic cell stimulation by mycobacterial Hsp70 is mediated through CCR5.
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.
Floto
R Andres
RA
Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK.
MacAry
Paul A
PA
Boname
Jessica M
JM
Mien
Tan Suet
TS
Kampmann
Beate
B
Hair
James R
JR
Huey
Oh Seen
OS
Houben
Edith N G
EN
Pieters
Jean
J
Day
Cheryl
C
Oehlmann
Wulf
W
Singh
Mahavir
M
Smith
Kenneth G C
KG
Lehner
Paul J
PJ
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
D001426:Bacterial Proteins; D015815:Cell Adhesion Molecules; D018840:HSP70 Heat-Shock Proteins; C444642:HSP70 protein, Mycobacterium tuberculosis; D015850:Interleukin-6; D019713:Receptors, CCR5