Heparan Sulfate–like Glycosaminoglycan Is a Cellular Receptor forChlamydia pneumoniae

Abstract

Chlamydia pneumoniae is an important human intracellular pathogen; however, the pathogenesis of C. pneumoniae infection is poorly understood, and the bacterial adherence mechanism to host cells is unknown. This study examined the role of glycosaminoglycans (GAGs) in the adhesion of C. pneumoniae to eukaryotic cells. Heparin and heparan sulfate were found to inhibit the attachment of C. pneumoniae to human epithelial cells. Reduction in infectivity resulted from the binding of heparin to the organism. Enzymatic removal of heparan sulfate moieties from the host cell surface led to a marked decrease in C. pneumoniae infectivity. Mutant CHO cell lines that were defective in heparan sulfate biosynthesis were less susceptible to C. pneumoniae infection than was the wild-type cell line. However, preincubation of the GAG-deficient CHO cells with exogenous heparin greatly increased infectivity.

Chlamydophila pneumoniae attachment and infection in low proteoglycan expressing human lymphoid Jurkat cells

“…Our study confirmed that following bacterial attachment, typical inclusions formed that were permissive to bacterial growth, resulting in increased infectious progenies in [17][18][19][20][21][22]. Heparin, which forms the majority of GAGs, also plays a critical role in host cells as a receptor for the attachment of the other pathogens such as Bordetella pertussis [35], Hemophilus influenzae [36] or Neisseria gonorrhoeae [37].…”

“…Heparin independent attachment and host invasion has also been described for the C. trachomatis LGV invasive serotype causing a systemic disease, but not for any other serotypes [17][18][19][20][21][22]. This suggests that a heparin-independent attachment mechanism is useful for a pathogen to effectively spread from local lesions, such as the genital tract in this case, to other distinct lymphoid tissue, as observed in pelvic inflammatory disease [42].…”

“…Host cell attachment is critical in the pathogenic cycle of Chlamydia or Chlamydophila species and the underlying mechanisms involved have been extensively studied over many years using epithelial cells, such as HeLa cells, HEp-2 cells, or McCoy cells [17][18][19][20]. Data from these experiments suggest that heparin, which is the most common GAG, covalently attaches to the core proteins of PG expressed on the host cells and critically functions as a receptor against chlamydial adhesions, such as the outer membrane protein, OmcB [21] or stress protein, GroEL1 [22].…”

Chlamydial Intracellular Survival Strategies

“…In addition to heparan sulfate (Chen andStephens 1994, 1997;Chen et al 1996;Wuppermann et al 2001), the mannose receptor, the mannose 6-phosphate receptor, and the estrogen receptor have been proposed to act as host receptors for Chlamydia entry (reviewed in Cocchiaro and Valdivia 2009). Cell surfaceexposed protein disulfide isomerase (PDI) has also been shown to play an important role in EB attachment and entry (Abromaitis and Stephens 2009).…”

Chlamydia pneumoniae Stimulates IFN-γ Synthesis through MyD88-Dependent, TLR2- and TLR4-Independent Induction of IL-18 Release

“…In additional experiments aimed to assess the role of CD14 and TLRs for stimulation of cytokines, PBMC were preincubated (1 h, 37°C) with the various mAbs (anti-TLR4, anti-TLR2, or anti-CD14; 20 g/ml) before the stimulation with C. pneumoniae. As a heparan sulfate-like glycosaminoglycan has been shown to be a C. pneumoniae receptor on epithelial cells, the effect of blocking this potential chlamydial receptor with 500 g/ml heparin was investigated, as previously reported (15). To investigate the effects of de novo protein synthesis on IL-18 release, PBMC were stimulated with C. pneumoniae in the presence of 10 g/ml cycloheximide (16).…”