Exosomal Hsp70 induces a pro-inflammatory response to foreign particles including mycobacteria.
BACKGROUND
Exosomes are endosome-derived vesicles that are released when multi-vesicular bodies (MVBs) fuse with the plasma membrane. Exosomes released from mycobacteria-infected cells have recently been shown to be pro-inflammatory. A prominent host molecule that is found within these exosomes is Hsp70, a member of the heat-shock family of proteins.


RESULTS
We first characterized the exosomes purified from control and mycobacteria-infected cells. We found that relative to uninfected cells, macrophages infected with M. smegmatis and M. avium release more exosomes and the exosomes they released had more Hsp70 on their surface. Both exosomes and exogenous Hsp70 treatment of macrophages led to NF-kappaB activation and TNFalpha release in uninfected macrophages; Hsp70 levels were elevated in mycobacteria-infected cells. Macrophage treatment with Hsp70 also led to increase in the phagocytosis and maturation of latex-bead phagosomes. Finally, Hsp70 pre-incubation of M. smegmatis- and M. avium-infected cells led to increased phago-lysosome fusion, as well as more killing of mycobacteria within macrophages.


CONCLUSIONS
Our results fit into an emerging concept whereby exosomes-containing Hsp70 are effective inducers of inflammation, also in response to mycobacterial infection.
Anand
Paras K
PK
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany. Paras.Anand@stjude.org
Anand
Ellis
E
Bleck
Christopher K E
CK
Anes
Elsa
E
Griffiths
Gareth
G
D000818:Animals; D002460:Cell Line; D055354:Exosomes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D007249:Inflammation / Q000209:etiology* / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D009161:Mycobacterium / Q000276:immunology*; D009164:Mycobacterium Infections / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010587:Phagocytosis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha
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