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| MACROPHAGE PHAGOCYTOSIS OF VIRULENT BUT NOT ATTENUATED STRAINS OF MYCOBACTERIUM-TUBERCULOSIS IS MEDIATED BY MANNOSE RECEPTORS IN ADDITION TO COMPLEMENT RECEPTORS |
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| Author(s): SCHLESINGER LS |
| Source: JOURNAL OF IMMUNOLOGY Volume: 150 Issue: 7 Pages: 2920-2930 Published: APR 1 1993 |
| Times Cited: 267 References: 49 |
| Abstract: We have examined macrophage receptors that mediate phagocytosis of virulent strains (Erdman and H37Rv) and an attenuated strain (H37Ra) of the intracellular pathogen, Mycobacterium tuberculosis. Adherence of the three strains to monocyte-derived macrophages (MDM) is markedly enhanced (>threefold) in the presence of low levels of fresh serum and requires heat-labile serum components because heat inactivation of serum reduces adherence by 65 +/- 5 to 71 +/- 2%. In the presence and absence of serum, adherence of the three strains to MDM is comparable. By electron microscopy, all bacteria are ingested and reside in phagosomes. C receptors (CR) play an important role in adherence of the three strains to MDM in the presence and absence of serum. mAb against CR1, CR3, and CR4 inhibit adherence of Erdman M. tuberculosis in fresh serum by 75 +/- 3% and inhibit the low level of adherence of Erdman (71 +/- 13%), H37Rv (72 +/- 1%), and H37Ra (64 +/- 14%) M. tuberculosis in the absence of serum. Mannose receptors (MR) play an important role in mediating macrophage adherence of the virulent strains but not the attenuated strain of M. tuberculosis. Preincubation of MDM with soluble mannan or mannose-BSA consistently and significantly inhibits adherence of Erdman and H37Rv (up to 60 +/- 7%) but not H37Ra (0 +/- 1 to 5 +/- 5% enhancement of adherence) in the absence of serum. Down-modulation of macrophage MR on mannan substrates inhibits adherence of Erdman (52 +/- 8%) and H37Rv (55 +/- 6%) but not H37Ra (2 +/- 2% enhancement of adherence). Preincubation of MDM with soluble N-acetylglucosamine-BSA also significantly inhibits adherence of the virulent strains (42 +/- 3%). Preincubation of MDM with glucose-BSA minimally inhibits adherence of the three strains (2 +/- 4 to 12 +/- 5%). Anti-MR antibody inhibits adherence of Erdman (57 +/- 2%) and H37Rv (44 +/- 4%) but not H37Ra (4 +/- 5% enhancement of adherence). Inhibition of adherence of zymosan was comparable with that seen with virulent strains of M. tuberculosis in these studies. Down-modulation of macrophage MR also inhibits adherence of Erdman (48 +/- 9%) and H37Rv (20 +/- 2%) in the presence of serum. Simultaneous blockade of MR and CR does not further inhibit adherence of the virulent M. tuberculosis strains over that seen with blocking CR alone. This study demonstrates that serum components such as C and CR on macrophages play important roles in mediating phagocytosis of both virulent and attenuated strains of M. tuberculosis but that MR also play an important role in phagocytosis of virulent strains. Differences in phagocytosis between virulent and attenuated M. tuberculosis strains will enhance our understanding of a pathway that may influence intracellular survival. |
| Document Type: Article |
| Language: English |
| Reprint Address: SCHLESINGER, LS (reprint author), UNIV IOWA, DEPT INTERNAL MED, 200 HAWKINS DR, SW54-GH, IOWA CITY, IA 52242 USA |
Addresses:
1. VET ADM MED CTR, DEPT INTERNAL MED, IOWA CITY, IA 52240 USA |
| Publisher: AMER ASSOC IMMUNOLOGISTS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Immunology |
| IDS Number: KT805 |
| ISSN: 0022-1767 |
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