SELECTIVE RECEPTOR BLOCKADE DURING PHAGOCYTOSIS DOES NOT ALTER THE SURVIVAL AND GROWTH OF MYCOBACTERIUM-TUBERCULOSIS IN HUMAN MACROPHAGES

Mycobacterium tuberculosis survives and replicates within human macrop hages, but the mechanisms whereby tubercle bacilli resist killing are incompletely understood. We tested the general model in which M. tuber culosis evades killing by entering naive macrophages through receptors that are unable to activate cellular microbicidal activities. Complem ent receptor types 1 (CR1), 3 (CR3), and 4 (CR4) were blocked with mon oclonal antibodies, and mannose receptors were blocked with a competit ive ligand, mannosylated bovine serum albumin (MESA). Survival and rep lication of M. tuberculosis (Erdman) were evaluated after the bacteria were phagocytosed in the presence of blocking agents (directing bindi ng to the unblocked receptors). Although there was significant variati on in the growth rate of virulent M. tuberculosis in monocyte-derived macrophages from different donors, the intracellular survival and repl ication of mycobacteria were equivalent regardless of the receptor(s) used fbr binding and phagocytosis. We conclude that the mechanisms whe reby M. tuberculosis evades killing by human macrophages are independe nt of the receptor-mediated route of entry, and operate at one or more steps common to all entry pathways. Blocking complement and mannose r eceptors in combination did not completely abrogate binding of M. tube rculosis to macrophages. However, we found that two polyanionic scaven ger-receptor ligands exhibited a concentration-dependent ability to bl ock binding of M. tuberculosis to macrophages. Moreover, blocking clas s A scavenger receptors abrogated nearly all binding that persisted af ter blocking complement and mannose receptors. This indicates that cla ss A scavenger receptors are quantitatively important mediators of M. tuberculosis-macrophage interactions. M. tuberculosis has evolved mult iple mechanisms to promote its efficient entry into macrophages. This suggests that passage of the organism through macrophages may be an es sential early step in the pathogenesis of tuberculosis.