Role of chlamydial heat shock protein 60 in the stimulation of innate immune cells by Chlamydia pneumoniae.
Chlamydia pneumoniae stimulates potently maturation of and cytokine secretion by bone marrow-derived dendritic cells (BMDDC). BMDDC responses depend mainly on Toll-like receptor (TLR)2 and to a minor extent on TLR4. We demonstrate here using C. pneumoniae in an infectious model with the replication-permissive epithelial cell line HEp2 that HSP60 is produced in substantial amounts in chlamydial inclusions during infection. Electron microscopy of chlamydial inclusions revealed that HSP60 was mainly associated with reticulate bodies, but was also located in between the different chlamydial developmental forms. Supernatants of permissive HEp2 cells infected with C. pneumoniae contained soluble chlamydial HSP60 as demonstrated by Western blotting and were able to stimulate BMDDC of wild-type mice. The stimulatory capacity of culture supernatants correlated with the presence of chlamydial HSP60. In contrast, BMDDC from TLR4-mutant mice crossed to TLR2-deficient mice were not stimulated by the culture supernatant, indicating that chlamydial HSP60 but not cytokines, possibly secreted by infected HEp2 cells, are responsible for the observed stimulation of BMDDC. Purified recombinant HSP60 from C. pneumoniae stimulated BMDDC in a TLR2- and TLR4-dependent fashion similar to the whole microorganism. In summary, these data suggest chlamydial HSP60 as an important mediator of inflammatory responses during infection with C. pneumoniae.
Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Germany.
Clarissa Prazeres da
CP
Costa
Carsten J
CJ
Kirschning
Dirk
D
Busch
Susanne
S
Dürr
Luise
L
Jennen
Ulrich
U
Heinzmann
Sigrid
S
Prebeck
Hermann
H
Wagner
Thomas
T
Miethke
D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis / Q000502:physiology*; D001854:Bone Marrow Cells / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D018834:Chaperonin 60 / Q000032:analysis / Q000502:physiology*; D002690:Chlamydia Infections / Q000276:immunology*; D016993:Chlamydophila pneumoniae / Q000737:chemistry / Q000276:immunology* / Q000648:ultrastructure; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology*; D029721:Drosophila Proteins; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D007822:Laryngeal Neoplasms / Q000473:pathology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D021122:Protein Subunits / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001426:Bacterial Proteins; D018834:Chaperonin 60; D017077:Culture Media, Conditioned; D029721:Drosophila Proteins; D053762:Interleukin-12 Subunit p40; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12