The mannose receptor mediates uptake of pathogenic and nonpathogenic mycobacteria and bypasses bactericidal responses in human macrophages

The mannose receptor (MR) is involved in the phagocytosis of pathogenic mic roorganisms. Here we investigated its role in the bactericidal functions of human monocyte;derived macrophages (MDMs), using (i) trimannoside-bovine s erum albumin (BSA)-coated latex beads and zymosan as particulate ligands of the MR, and (ii) mannan and mannose-BSA as soluble ligands. We show that p hagocytosis of mannosylated latex beads did not elicit the production of O- 2(-). Zymosan, which is composed of alpha-mannan and beta-glucan, was inter nalized by the MR and a beta-glucan receptor, but the production of O-2(-) was triggered only by phagocytosis through the beta-glucan receptor. Activa tion and translocation of Hck, a Src family tyrosine kinase located on lyso somes, has previously been used as a marker of fusion between lysosomes and phagosomes in human neutrophils. In MDMs, Hck was activated and recruited to phagosomes containing zymosan later than LAMP-1 and CD63. Phagosomes con taining mannosylated latex beads fused with LAMP-1 and CD63 vesicles but no t with the Hck compartment, and the kinase was not activated. We also demon strate that the MR was unable to distinguish between nonpathogenic and path ogenic mycobacteria, as they were internalized at similar rates by this rec eptor, indicating that this route of entry cannot be considered as a differ ential determinant of the intracellular fate of mycobacteria. In conclusion , MR-dependent phagocytosis is coupled neither to the activation of NADPH o xidase nor to the maturation of phagosomes until fusion with the Hck compar tment and therefore constitutes a safe portal of entry for microorganisms.