Nonopsonic and opsonic association of Mycobacterium tuberculosis with resident alveolar macrophages is inefficient.
The association of Mycobacterium tuberculosis with alveolar macrophages (Mphi) in a serum-free environment is a crucial first step in the pathogenesis of this facultative intracellular pathogen. We present data demonstrating that freshly explanted alveolar Mphi do not efficiently bind M. tuberculosis in a serum-free system, although a small subpopulation of these Mphi (10-15%) can bind mycobacteria. In contrast, almost 100% of a peritoneal Mphi population bind mycobacteria under the same conditions. The poor binding of mycobacteria by alveolar Mphi does not reflect a general inability to associate with particles; binding and ingestion of latex beads and zymosan particles were comparable with that seen with peritoneal Mphi. Resident alveolar Mphi did not efficiently bind mycobacteria in the presence of serum and expressed poorly several Mphi surface receptors, including CR3. Furthermore, we demonstrate that bovine surfactant protein A does not enhance the association of M. tuberculosis with alveolar Mphi. Differentiation of alveolar Mphi in vitro resulted in increased expression of Mphi surface receptors and an increased capacity to bind mycobacteria in the presence and absence of serum. Evidence is presented that opsonic binding of M. tuberculosis by differentiated alveolar Mphi is mediated by complement and CR3, and that the poor binding by resident alveolar Mphi is due to their poor expression of CR3. The receptor mediating nonopsonic binding of M. tuberculosis to differentiated alveolar Mphi was not unequivocally identified in this study, but could also be CR3.
Stokes
R W
RW
Division of Infectious and Immunological Diseases, British Columbia's Children's Hospital, Vancouver, Canada. rstokes@cbdn.ca
Thorson
L M
LM
Speert
D P
DP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D001769:Blood / Q000382:microbiology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D003179:Complement C3b / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism; D009895:Opsonin Proteins / Q000097:blood*; D011510:Proteolipids / Q000494:pharmacology; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000494:pharmacology; D011951:Receptors, Complement / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D009895:Opsonin Proteins; D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D011951:Receptors, Complement; D003179:Complement C3b; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate