Role of chlamydial heat shock protein 60 in the stimulation of innate immune cells by Chlamydia pneumoniae

Abstract

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.

GroEL1, a Heat Shock Protein 60 of Chlamydia pneumoniae, Induces Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Expression in Endothelial Cells and Enhances Atherogenesis in Hypercholesterolemic Rabbits

“…pneumonia GroEL1 may induce innate immune responses in vitro via TLR2 and TLR4 (19). As shown in Fig.…”

Cellular Recognition of Tri-/Di-palmitoylated Peptides Is Independent from a Domain Encompassing the N-terminal Seven Leucine-rich Repeat (LRR)/LRR-like Motifs of TLR2

“…Lipidated OspA, a tripalmitoylated lipoprotein from B. burgdorferi, was from Dr. Dunn (Brookhaven National Laboratory, Upton, NY) and applied at 4.5 g/ml (26). Highly purified recombinant chlamydial HSP60 was as described previously (27) and applied at a concentration of 8 g/ml. Zymosan and phorbol 12-myristate 13-acetate (PMA) were from Sigma and applied at concentrations of 50 g/ml and 0.1 g/ml, respectively.…”

Chlamydial Intracellular Survival Strategies

“…As with most bacteria, Chlamydia infections are detected by host pattern recognition receptors (PRRs) that recognize chlamydial LPS via TLR4 (Ingalls et al 1995;Prebeck et al 2001Prebeck et al , 2003Heine et al 2003) and heat shock protein Hsp60 through TLR2 and TLR4 (Kol et al 1999(Kol et al , 2000Vabulas et al 2001;Bulut et al 2002;Costa et al 2002;Bulut et al 2009). TLR2 appears to be the predominant receptor required for an inflammatory response to infection (Prebeck et al 2001;Darville et al 2003;O'Connell et al 2006).…”