Chlamydia pneumoniae uses the mannose 6-phosphate/insulin-like growth factor 2 receptor for infection of endothelial cells.

Several mechanisms for attachment and entry of Chlamydia have been proposed. We previously determined that the major outer membrane protein of Chlamydia trachomatis is glycosylated with a high-mannose oligosaccharide, and a similar structure inhibited the attachment and infectivity of C. trachomatis in epithelial cells. Because insulin-like growth factor 2 (IGF2) was shown to enhance the infectivity of Chlamydia pneumoniae but not C. trachomatis in endothelial cells, a hapten inhibition assay was used to analyze whether the mannose 6-phosphate (M6P)/IGF2 receptor that also binds M6P could be involved in infection of endothelial cells (HMEC-1) by Chlamydia. M6P and mannose 6-phosphate-poly[N-(2-hydroxyethyl)-acrylamide] (M6P-PAA) inhibited the infectivity of C. pneumoniae AR-39, but not C. trachomatis serovar UW5 or L2, while mannan inhibited the growth of C. trachomatis, but not C. pneumoniae. Using metabolically labeled organisms incubated with cells at 4 degrees C (organisms attach but do not enter) or at 37 degrees C (organisms attach and are internalized), M6P-PAA was shown to inhibit attachment and internalization of C. pneumoniae in endothelial cells but did not inhibit attachment or internalization of C. trachomatis serovar E or L2. These findings indicate that C. pneumoniae can utilize the M6P/IGF2 receptor and that the use of this receptor for attachment and entry differs between C. pneumoniae and C. trachomatis.