Lipoarabinomannan inhibits nonopsonic binding of Mycobacterium tuberculosis to murine macrophages.
The initial phagocytic interaction between Mycobacterium tuberculosis and macrophages (M phi) in the lung is probably nonopsonic, which would mean that M phi receptors will bind directly to bacterial ligands without the involvement of serum opsonins. Lipoarabinomannan (LAM) is a major component of the cell wall of mycobacteria. The possibility that LAM is involved in the nonopsonic binding of M. tuberculosis to M phi was investigated by using competitive inhibition assays. LAM inhibited binding of M. tuberculosis to murine peritoneal M phi in a dose-dependent manner. LAM also inhibited the binding of Mycobacterium avium and Mycobacterium bovis BCG to M phi. Phosphatidylinositol mannoside and lipomannan have the same phosphatidylinositol (PI) moiety as LAM, but differ in their glycosylation patterns. Both molecules inhibited binding of M. tuberculosis to M phi. Deacylation of LAM abrogated its capacity to inhibit binding of M. tuberculosis to M phi. These observations indicated that it was the PI moiety of LAM that was important in mediating its inhibitory properties. In support of this hypothesis, commercial PI was shown to inhibit the binding of M. tuberculosis to M phi. Our results suggest that cellfree LAM is able to inhibit the binding of mycobacteria to M phi, but that it does not do so by competing with any interaction between M phi receptors and cell-associated LAM, because the PI end of the molecule is believed to be anchored in the bacterial plasma membrane, and therefore not available as a ligand on the cell surface. However, LAM that is released from M. tuberculosis in the course of its active replication during infection may be able to interfere with the phagocytic clearance of mycobacteria.
Stokes
R W
RW
Division of Infectious and Immunologic Diseases, British Columbia's Children's Hospital, Vancouver, Canada.
Speert
D P
DP
D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009162:Mycobacterium avium / Q000378:metabolism; D009163:Mycobacterium bovis / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D010587:Phagocytosis / Q000187:drug effects*; D010716:Phosphatidylinositols / Q000494:pharmacology; D011951:Receptors, Complement / Q000378:metabolism; D014774:Virulence
D008070:Lipopolysaccharides; D010716:Phosphatidylinositols; D011951:Receptors, Complement; C050016:lipoarabinomannan; C034154:phosphatidylinositol mannoside