TY - JOUR
T1 - Mycobacteria-macrophage interactions
T2 - Macrophage phenotype determines the nonopsonic binding of Mycobacterium tuberculosis to murine macrophages
AU - Stokes, R. W.
AU - Haidl, I. D.
AU - Jefferies, W. A.
AU - Speert, D. P.
PY - 1993
Y1 - 1993
N2 - During tuberculosis, host defenses may be determined, in part, by the capacity of resident, elicited, and activated macrophages to bind and ingest Mycobacterium tuberculosis. We have investigated the mechanism by which macrophages bind M. tuberculosis and other mycobacteria in a serum-free system. The extent of binding of M. tuberculosis to macrophages was dependent on the phenotype of the macrophage; thioglycollate-elicited and immune- activated macrophages bound mycobacteria poorly, whereas resident macrophages bound mycobacteria efficiently. Within 'freshly' explanted macrophage populations (from 2 to 24 h in vitro) poor binding of mycobacteria correlated with poor binding of C3bi-coated particles, but not with variations in the level of complement receptor 3 (CR3) expression. Induction of C3bi-coated particle binding in thioglycollate-elicited macrophages by PMA was not accompanied by enhanced M. tuberculosis binding. Inhibition of M. tuberculosis binding by resident macrophages could only be achieved using a mAb recognizing an epitope within CR3 distinct from that which recognizes C3bi. Our results suggest that nonopsonic binding of M. tuberculosis is mediated by a site within CR3, which is distinct from the C3bi binding site. In addition, we show a variation in the capacity of different macrophage phenotypes to bind mycobacteria nonopsonically. These data suggest that heterogeneity in macrophage-mediated clearance of M. tuberculosis may be a significant factor in the progression of tuberculosis.
AB - During tuberculosis, host defenses may be determined, in part, by the capacity of resident, elicited, and activated macrophages to bind and ingest Mycobacterium tuberculosis. We have investigated the mechanism by which macrophages bind M. tuberculosis and other mycobacteria in a serum-free system. The extent of binding of M. tuberculosis to macrophages was dependent on the phenotype of the macrophage; thioglycollate-elicited and immune- activated macrophages bound mycobacteria poorly, whereas resident macrophages bound mycobacteria efficiently. Within 'freshly' explanted macrophage populations (from 2 to 24 h in vitro) poor binding of mycobacteria correlated with poor binding of C3bi-coated particles, but not with variations in the level of complement receptor 3 (CR3) expression. Induction of C3bi-coated particle binding in thioglycollate-elicited macrophages by PMA was not accompanied by enhanced M. tuberculosis binding. Inhibition of M. tuberculosis binding by resident macrophages could only be achieved using a mAb recognizing an epitope within CR3 distinct from that which recognizes C3bi. Our results suggest that nonopsonic binding of M. tuberculosis is mediated by a site within CR3, which is distinct from the C3bi binding site. In addition, we show a variation in the capacity of different macrophage phenotypes to bind mycobacteria nonopsonically. These data suggest that heterogeneity in macrophage-mediated clearance of M. tuberculosis may be a significant factor in the progression of tuberculosis.
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M3 - Article
C2 - 8258711
AN - SCOPUS:0027137823
SN - 0022-1767
VL - 151
SP - 7067
EP - 7076
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -