Complement activation by mycoloyl glycolipids from Mycobacterium tuberculosis and Rhodococcus ruber.
In this study, we examined complement activation by mycoloyl glycolipids (MGL) such as trehalose-6,6'-dimycolate (TDM), often termed cord factor, and trehalose-6-monomycolate from Mycobacterium tuberculosis and Rhodococcus ruber, and also examined the effect of complement binding to MGL on phagocytosis by human monocytes. TDM and TMM, but not glucose mycolate, mannose mycolate or fructose mycolate which differ from TMM only in carbohydrate moiety, exhibited complement activation. TDM and TMM of M.tuberculosis exhibited stronger complement activation than those of R.ruber, the mycolic acids of which are much shorter than those of M.tuberculosis. Neither mycolic acids nor trehalose, which are products of TDM and TMM by hydrolytic cleavage, exhibited no complement activation. TDM activated complement through the alternative pathway, since supplementation with C4-deficient serum completely restored classical pathway-mediated hemolytic activity of complement which had been previously consumed by TDM. Next, we examined the effects of TDM and TMM on phagocytosis by human monocytes. Coating of heat-killed Staphylococcus aureus cells with TDM or TMM did not enhance their phagocytosis by monocytes, while, in the presence of complement, phagocytosis of these cells increased significantly. These findings suggest that TDM and TMM act as virulence factors that enhance the entry of mycobacteria into phagocytes via binding of C3 through activation of the alternative complement pathway.
Yasuda
K
K
Department of Bacteriology, Osaka City University Medical School.
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003167:Complement Activation / Q000502:physiology*; D003311:Cord Factors / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D009000:Monocytes / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000737:chemistry; D010587:Phagocytosis / Q000187:drug effects; D012240:Rhodococcus / Q000737:chemistry
D000276:Adjuvants, Immunologic; D003311:Cord Factors