• Volume 69 , Number 4
  • Page: 341–8

Biochemical aspects of Mycobacterium leprae binding proteins: a review of their role in pathogenesis

Lavanya M. Suneetha; Deena Vardhini; Sujai Suneetha; A. S. Balasubramanian; C. K. Job; David Scollard

Editorial opinions expressed are those of the writers.

Leprosy is one of the oldest human neurological diseases resulting from infection with an obligate, intracellular pathogen Mycobacterium leprae. Neuropathy in leprosy is usually a subacute, demyelinating and remitting event involving the cutaneous and trunk nerves. The invasion of Schwann cells and axons by M. leprae leads to de-myelination and axonal degeneration.1

The specificity of bacteria-host cell interaction and the pattern of tissue distribution of host cell receptors determines the tissues which are ultimately infected by a pathogen.2 A recent advance in understanding the pathogenesis of leprosy- in particular, the affinity of M. leprae to the Schwann cell- is the discovery of host Schwann cell proteins that bind to M. leprae. Receptormediated mechanisms have been suggested to be involved in Schwann cell-M. leprae interaction. Rambukkanna, et al. (1998), showed that laminin (LN)-α dystroglycan (a DG) bridge present in the basal lamina of Schwann cells could mediate the entry of M. leprae: Subsequently, a complementary 21-kDa protein present on the M. leprae surface was shown to bind to laminin, explaining the neural affinity of M. leprae* However, other proteins such as fibronectin (FN) 6,7 β- p integrin6 and a 25-kDa glycoprotein 8 have also been shown to bind to M. leprae.

Although M. leprae is known to bind to different proteins, their relative role in pathogenesis is not yet clearly defined. Here we have reviewed some of the biochemical aspects of M. leprae binding proteins, and have followed with a discussion of the tissue proteins that were found to bind to M. leprae.



Byrd, et al. (1993),6 carried out experiments on nasal septal cell interactions with M. leprae. The methodology involved studies on M. leprae binding to nasal epithelial cells in the presence and the absence of various modulators, such as mannoside, fj galactoside, fibronectin, antibodies to fibronectin, CD1 la, CD29, CD54 and also to a peptide gly-arg-gly-arg-ser (The Table). The result was evaluated either by an ELISA or visual observation of M. leprae binding. The study showed that M. leprae binds to nasal epithelial cells after binding to fibronectin, using (3-integrins as receptors.The corresponding component on M. leprae, which binds to fibronectin (Fibronectin binding protein FAP) has been identified and characterized. It is a protein of 29.5-kDa and has sequence homologies with other mycobacteria- M. vaccae, M. avium and M. tuberculosis. Fibronectin significantly enhanced both attachment and ingestion of M. leprae by T24 epithelial and JS1 Schwannoma cell lines.



Interestingly, further experiments showed that even in the absence of soluble fibronectin M. leprae was found to bind to the nasal epithelial cells, suggesting an independent β-integrin-M. leprae interaction. β-Integrin is a known receptor for fibronectin.6 Therefore, fibronectin-integrin mediated binding mechanisms could play a role in the pathogenesis of cells expressing these proteins.

Fibronectin is also known as cold insoluble globulin (CIG) with a molecular weight of 262.05-kDa. It binds to cell surfaces and to various compounds including collagen, fibrin, heparin, DNA and actin. FNs are involved in cell adhesion, cell motility, opsonization, wound healing and maintenance of cell shape.10,11,12 FN occurs mostly as heterodimers, multimers of alternatively spliced variants, connected by 2 distillide bonds near the carboxyl ends. Plasma FN (soluble dimeric form) is secreted by hepatocytes and cellular FN (dimeric or cross linked multimerie forms) is synthesized by fibroblasts, epithelial and other cell types.12, 13 FN is deposited as fibrils in the extracellular matrix. Phosphorylation, glycosylation and sulfation sites are present in this protein.13

β-Integrin (also known as fibronectin receptor, Beta sub unit CD29 or integrin VLA4 beta sub unit) has a molecular weight of 88.465-kDa. It is a type-I membrane protein and is a receptor for libronectin, laminin and vitronectin. It is widely expressed in skin, liver, skeletal muscle, cardiac muscle, placenta, umbilical vein, endothelial cells, neuroblastoma cells and astrocytoma cells.  It is a transmembrane receptor protein present in the extracellular matrix and cytoskeleton. This protein is phosphorylated and glycosylated.18



The laminin-2 isoform is present at the Schwann cellaxon units, in the peripheral nerves. It is composed of α2 heavy chains together with β1 and ϒl light chains. However, the chain has a tissue restricted distribution, predominately expressed in the basal lamina of Schwann cells and muscles, while the (β1 and ү l chains have a wide range of distribution.19-23 Laminin-2 or laminin merosin heavy chain (LNα2G) has a molecular weight of 342.766-kDa. This glycoprotein binds to cells via a high affinity receptor such as adystroglycan (αDG) or p-integrin. It is present in the placenta, striated muscle, peripheral nerve, cardiac muscle, pancreas, lung, spleen, kidney, adrenal gland, skin, testis, meninges, choroid plexus and brain, but is not present in liver, thymus or bone.24,25

αDystroglycan or dystrophin-associated glycoprotein (molecular weight 97.5-kDa) is a type-I extracellular membrane protein. This protein has phosphorylation and glycosylation sites. It is present in a variety of adult and fetal tissue. It forms a dystrophin-associated protein complex (DAPC), which may link the cytoskeleton to the extracellular matrix. αDG not only binds to M. leprae but also to several types of arena viruses [lymphocytic choriomeningitis virus (LCMV), Lassa fever, Oliveros and Mobala viruses26].

Dystroglycan is a laminin receptor encoded by a single gene and cleaved by posttranslational processing into two proteins, the peripheral membrane αDG and transmembrane PDG.27 While aDG interacts with laminin-2 in the basal lamina, (βDG appears to bind to dystrophin-containing cytoskeletal proteins in muscles and peripheral nerve. The loss or a defect of laminin 2-aDG interaction causes certain types of muscular dystrophy and peripheral neuropathy.4- 2 Experiments were carried out on immobilized αDG binding to M. leprae in the presence of different modulators. This binding was assessed by ELISA. The other experiments were on Schwann cell cultures with and without modulators such as human FN, type IV collagen, murine Engelbreth-Holm-Swarm-tumor laminin (EHS-tumor LN), etc. (The Table).4,30 The results showed that αDG participates in LNα2G mediated M. leprae interaction with Schwann cells. M. leprae binding to LNα2G was increased by >95% with increased concentration of LNα2G. However,similar results were also obtained with a mixture of LN-2 and LN-4. Glycosylation and Ca+ ions seem to regulate αDG's interaction with M. leprae through the LNα2G domain.4 Schwann cell experiments in the presence of antibodies to αDG did not completely inhibit binding. Additionally, purified αDG was unable to compete 100% for LNα2G-mediated binding suggesting other Schwann cell laminin receptors. Hence, the experimental data on laminin and cxDG interaction do not exclude other mechanisms of M. leprae binding to Schwann cells.

Among the several forms of integrins the a6(34 integrins. particularly the (34 subunit, appear to be involved in M. leprae binding. Further experimentation by Ram-bukkanna, et al. (1998),4 showed that the HBL-100 and Cos-7 cells which strongly express aβ4 integrins- the laminin receptors- exhibited significant adherence of M. leprae, whereas erythroleukemic k562 cells which lack known LN receptors including a6β4 integrins showed negligible binding. Hence, LNα2G-associated M. leprae-Schwann cell binding is also mediated by 016(34 integrin receptors on Schwann cells.



Protein phosphorylation is a posttranslational modification of proteins important insignal transduction and is prominent innerve tissue.32,33 Recent studies have shownthe involvement of phosphorylation eventsin binding of bacteria to host cells.34-36 Earlier studies have shown that purified M. lepra ecould inhibit the phosphorylation of 28-kDa to 30-kDa protein of the rat peripheral nerve.37 One of the mechanisms proposed for this observation is the interaction between M. leprae and phosphorylated proteins. Binding experiments revealed that M. leprae bound to a major 28-kDa to 30-kDa protein and a few minor proteins of 45-kDa to 50-kDa range. However. M. bovis and E. coli also bound to these phosphorylated proteins but to a significantly lesser extent.38 Similar observations were found with phosphorylated human peripheral nerve binding experiments (The Table). Biochemical characterizations of the 25,-kDa protein showed that it is a major phosphorylated protein of the human peripheral nerve, which was found to bind to M. leprae8. It is a complex carbohydrate containing protein. When Triton X-100 was excluded in the homogenization buffer, the yield of this protein was negligible suggesting that it may be a membrane bound protein.

Protein phosphorylation and autoradiography studies of the human peripheral nerve proteins showed a major band of a range of 23-kDa to 28-kDa. This could be due to a mobility shift caused by heterogeneous phosphorylated species.39 Binding of this 25-kDa glycoprotein to the lectins, artocarpin and concanavalin A to a major extent, and to winged bean agglutinin andja-calin to a minor extent, indicated that the lectin binding epitopes have branched N-linked oligosaccharides with mannose and galactose residues similar to that reported for the P0 protein of human peripheral nerve myelin.8 Earlier, other groups had extensively studied the phosphorylation andglycosylation of the myelin protein (PO)from human and rat peripheral nerve, usingSDS-PAGE and autoradiography.41,42Hence, the biochemical characteristics ofthe 25-kDa protein namely its molecularweight, carbohydrate content and phospho-rylatable nature are similar to those reported for the PO protein of peripheral nervemyelin:43-46 Further work recently carriedout in our laboratory has immunologicallyidentified the 25-kDa protein as PO of theperipheral nerve myelin (unpublished ob-servation). M. leprae binding to PO (the 25-LDa glycoprotein) could have a major im-plication as it would throw light on the M.leprae-target interaction and consequentpathological manifestations such as demyelination andaxonal degeneration. PO is a highly abundant, phosphorylated and glycosylatedmembrane protein of the human peripheralnerve that has two major domains: anextracellular immunoglobin-like domain and an intracellular basic region.47 It isknown to be involved in myelin compaction.48,49



Other experiments have been carried out in different cells on M. leprae binding and internalization. A major difficulty in interpreting all of these reports is that the conditions for the in vitro binding studies were different with respect to the source of Schwann cells or the source, storage and pre-treatment of M. leprae. Glial cell lines display no specificity in the uptake of M. leprae, whereas Lewis TC98 Schwann cells which mimic mouse Schwann cells show a preferential uptake of M. leprae, and not heat-killed M. leprae or M. lepraemurium. Observations on human nerve-teased fiber preparation showed that Schwann cells engulfed M. leprae, M. tuberculosis and carbon particles without any discrimination. In another study, M. leprae uptake was blocked by anti-mycobacterial antibodies directed against phenolic glycolipid-1 in disassociated Schwann cells suggesting the involvement of phenolic glycolipid. LAM (lipoarabinomannan) and PGL-I (phenolic glycolipid-I) of M.leprae has been shown to bind to macrophages and human peripheral nerve.53,54,55 Binding and internalization of M. leprae by human endothelial cells has recently been demonstrated, but the mycobacterial and host cell molecules involved have yet to be identified.56

Considering these varied observations on tissue culture and human nerve experiments, binding and internalization may not necessarily be directly related, and each may or may not have significance in pathogenesis and neural predilection. That is, in simple biochemical terms, all binding may not lead to internalization and all internalization may not mean neural predilection.



α-Dystroglycan, laminin-2, β-integrin, fibronectin and the 25-kDa glycoprotein (P0) are all membrane glycoproteins of phos-phorylatable nature present in different tissues, and they all have an affinity to bind to Mycobacterium leprae. The only protein, with nerve tissue specificity, is PO and whether it adds on to the present understanding of M. leprae's neural predilection needs further experimentation. The molecular mechanisms of the relative binding affinities of M. leprae-b'md'ing proteins, their specificity of binding to M. leprae, their interaction with other membrane glycoprotein complex components, influence of phosphorylation, glycosylation. other modulators such as calcium, the complementary components on the surface of M. leprae (FAP/21-kDa surface protein/ PGL/any other membrane components), and also the host/bacterial signalling mechanisms which could stimulate M. leprae to multiply in Schwann cells are areas which need further research.

Since we now have the whole M. leprae gene sequence, computational studies on homology modelling of M. leprae-binding proteins and their ligands on M. leprae may provide new directions in understanding the pathogenesis of nerve injury in leprosy.

Acknowledgment. We acknowledge the information obtained from SWISS-PROT data bank searches for the M. leprae binding proteins. We thank E. Ramesh for helping us prepare this manuscript, and to LEPRA and MRC UK for financial assistance.


- Lavanya M. Suneetha, Ph.D.
Deena Vardhini, Ph.D.
Sujai Suneetha, DCP, Ph.D.

Blue Peter Research Centre,
Near TEC Building, Cherlapally
Hyderabad 501 301, AP, India

- Balasubramanian A. S., Ph.D.

Professor of Biochemistry (Rtd.)
Christian Medical College & Hospital

Vellore-632006, India

- Job C. K., M.D., FRC Path

Consultant Pathologist
St. Thomas Hospital & Leprosy Centre

Chettupattu. Tamil Nadu, 606 801, India

- David Scollard, M.D., Ph.D.

Chief Research Pathology
National Hansen's Disease Programs at
Louisiana State University
Baton Rouge, Louisiana, USA


1. Job. C. K. Nerve damage in leprosy. Int. J. Lepr.571(1989)532-539.

2. Isberg, R. R. Discrimination between intracellularuptake and surface adhesion of bacterial pathogens.Science 252(1991)934-938.

3. Rambukkanna, A. How does Microbacterium leprae target the peripheral nervous system. Trends Microbiol. 8(2000)23-28.

4. Rambukkanna. A., Yamada, H., Zanazzi. G.,Mathus, T., Salzer, J. K., Yurchenco, P. D.. Campbell,K. P. and Fischetti. V. A. Role of α dystroglycan as aSchwalm cell receptor for M. leprae. Science 282(1998) 2076-2079.

5. Shimoji, Y.. Vincent, N. G., Matsumara, K., Fischetti. V. A. and Rambukkanna. A. A. 21-k Da surfaceprotein of Mycobacterium leprae binds peripheralnerve laminin-2 and mediates Schwalm cell inProc. Natl. Acad. Sci. 96 (1999)9857-9862.

6. Byrd. S. R., Gelber. R. and Bermudez, L. E. Roleof soluble libronectin and li-integrin receptors in thebinding of Mycobacterium leprae to nasal epithelialcells. CAM. Inummol. Immunopathol. 69(1993)266-271.

7.Mastek, M., Clark-Curtiss, J. E., Ratliff, J. L. andBrown, E. J. A Mycobacterium leprae gene encodingfibronectin binding is used for efficient invasion of epithelial cells and Schwann cells. Infect. Immun. 63(1995)2652-2657.

8. Suneetha, L. M.. Satish. P. R., Korula, R. J.,Suneetha, S. K., Job, C. K. and Balasubramanian, A. S.Mycobacterium leprae binds to a 25-kDa phosphorylated glycoprotein of human peripheral nerve. Neurochem. Res. 23(1998)907-911.

9. Ratliff, T. R., McCarthy, R., Telly, W. B. and Brown, E. J. Purification of a mycobacterial adhesionfor fibronectin. Infect. Immun. 61(1993)1889-1894.

10. McKeown-Longo, P. J. Fibronectin-cell surfaceinteraction. Rev. Infect. Dis. 9(1987)5322-5334.

11. Klultinger, J. L., Kelly, N. M., Josh, B. H. andHancock, R. E. Fibronectin as an enhancer of non-opsonic phagocytosis of Pseudomonas aeruginosa bymacrophages. Infect. Immun. 57(1989)2782-2785.

12. Hynes, R. 0. and Yamada, K. M. Fibronectins:multifunctional modular glycoproteins. J. Cell. Biol.95(1982)369-377.

13. McKeown-Longo, P. J. and Mosher, D. J. Inter-action of the 70,000 mol wt aminoterminal fragment offibronectin with the matrix assembly receptor of fi-broblasts. J. Cell. Biol. 100(.1985)364-374.

14. Sharma, A., Askari, J. A., Humphries, M. J.,Jones, E. Y. and Stuart, D. I. Crystal structure of a hep-arin and integrin binding segment of human FN.EMBO. J. 18 (1999)14468-1479.

15.Isberg, R. R. and Leong, J. M. Multiple Beta 1Integrins are receptors for invasion, a protein that pro-motes bacterial penetration into the mammalian cells.Cell 60(1990)861-871.

16. Zhidkova, N. I., Belkin, A. M. and Mayne, R.Novel isoform of 13 I integrin expressed in skeletal andcardiac muscle. Biochem. Biophys. Res. Commun.214(1995)279-285.

17. Hynes, R. 0. Integrins, versatility. modulation,and signalling in cell adhesion. Cell 69(1992)11-25.

18. Argraves, W. S.. Suzuki. S., Arai. H., Thompson,K., Pierschbacher. M. D. and Ruoslahti, E. Amino acidsequence of the human libronectin receptor. J. Cell.Biol. 105(1987)1183-1190.

19. Engvall, E., Earwicker. D., Day, A., Muir, D.,Mauthrope, M. and Paulsson. M. Merosin promotescell attachment and neurite outgrowth and is a compo-nent of the neurite-promoting factor of RN22 Schwan-noma cells. Exp. Cell. Res. 198 (1992)115-123.

20. Engvall, E. Laminin variants: why, where, andwhen? Kidney Int. 43(1993)2-6.

21.Combrooks, C. J., Carey. D. J.. McDonald. J. A.,Timple, R. and Bunge, R. P hi vivo and if/ vitm obser-vations on laminin production by Schwann cells. Proc.Natl. Acad. Sci. 80(1983)3850-3854.

22..Jaakkola. S., Savunen, 0., Halme, T., Uitto, J.and Pehonen. J. Basement membranes during develop-ment of human nerve: Schwann cells and perinueralcells display marked changes in their expression pro-files for laminin subunits and beta I and beta 4 inte-grins. J. Neurocytol. Cell 60(1993)253-261.

23. EngvaIL E. and Wewer, U. M. Domains oflaminin. J. Cell. Biochem. 61(1996)493-501.

24. Burgeson. R. E., Chiquet. M.. Duetzmann. R..Ekblom, P., Engel, J., Kleinman, H., Martin. G. R.,Meneguzzi, G.. Paulsson, M., Sillies, J., el al. A newnomenclature for the laminins. Matrix Biol. 14(1994)209-211.

25. Timple, R. and Brown.,I. C. The laminins. MatrixBiol. 14(1994)275-281.

26.Cao, W., Henry, M. D., Borrow, P., Yamada. H.,Elder, J. H.. Ravkov, E. V., Nichol, S. T., Compans, R.W., Campbell. K. P. and Oldstone, M. B. A. identifica-tion of a dystroglycan as a receptor for lymphocyticchoriomeningitis virus and lassa virus. Science 282(1998) 2079-2081.

27. Ibraghimov-Beskrovnaya, 0. Primary structureof dystrophin-associated glycoproteins linking dys-trophin to the extracellular matrix. Nature 355 ( 1992)696-702.

28. Ervasti, J. M. and Campbell, K. P. A role for thedystrophin glycoprotein complex as a transmembranelinker between laminin and actin. J. Cell. Biol. 122(1993)1121-1130.

29. Campbell. K. P. Three muscular dystrophies: lossof cytoskeleton-matrix linkage. Cell 80(1995)675-679.

30. Rambukkanna, A., Salzer, J. L., Yurchenco, P. D.and Toomanen. E. I. Neural targeting of Mycobacte-rium Icimte mediated by the G domain or the Laminin-(92 chain. Cell 88 11997)811-821.

31.Niessen, C. M., Cremona, O., Daams, H., Ferraresi, S., Sonnenberg, A. and Marchisio, P. C. Expres-sion of the integrin a6[34 in peripheral nerves: localization in Schwann and perineural cells and differentvariants of the 134 subunit. J. Cell. Sci. 107(1994)543-552.

32. Edelman, A. M., Blumenthal, D. K. and Krebs,E. G. Protein serine/threonine kinases. Ann. Rev.Biochem. 56(1987)567-613.

33. Eichberg, J. and Iyer, S. Phosphorylation ofmyelin proteins: recent advances. Neurochem. Res. 21(1996)527-535.

34. Bermudez, L. E. and Young, L. S. Factors affect-ing invasion of HT-29 and Hep-2 epithelial cells by or-ganisms of the Mycobacterium avium complex. Infect.Immun. 62(1994)2021-2026.

35.Murakami, Y., Hanazawa, S., Watanabe, A., Na-ganuma, K., lwasaka, H., Kawakami, K. and Kitano,S. Prophyromonas ginivalis fimbriae induce 68-kDaphosphorylated protei a in macrophages. Infect. 1th-mun. 62(1994) 5242-5246.

36. Rosenshine, I., Ruschkowski, S., Fouhister, V.and Finlay, B. B. Salmonella typhimurium invasionof epithelial cells: role of induced host tyrosine protein phosphorylation. Infect. Immun. 62(1994)4969-4974.

37. Suneetha, L. M., Job, C. K. and Balasubramanian, A. S. Effect of Mycobacterium lepnie on periph-eral nerve protein phosphorylation- A preliminarystudy. Int. J. Lepr. 64(1996)333-335.

38. Suneetha, L. M., Satish, P. R., Suneetha, S. K.,Job, C. K. and Balasubramanian. A. S. M. leprae bindsto a 28-30 kDa phosphorylated glycoprotein of rat peripheral nerve. Int. Lepr. 65(1997)352-356.

39. Suneetha, L. M.. Korula, R. J. and Balasubra-manian, A. S. Protein phosphorylation in human peripheral nerve: altered phosphorylation of a 25-kDaglycoprotein in leprosy. Neurochem. Res. 21(1996)707-712.

40. Burger,Burger, D., Perruisseau, G., Simon, M. md Sleek, A. J. Comparison of the N-linked oligosaccharidestructures of the two major human myelin glycopro-teins MAG and PO. Assessment of the structures bear-ing the epitope for HNK-1 and human monoclonalIgM found in demyelinating neuropathy. J. Neurochem. 58(1992)845-853.

41. Hilmi. S., Fournier. M.. Valeins, H., Gandar, C. J.and Bonnet. J. Myelin PO alycoprotein: identificationof the phosphorylated site in vi/re and in vivo by en-dogenous kinases. J. Neurochem. 64(1995)902-907.

42.Eichberg, J. and lyer, S. Phosphorylation ofmyelin proteins: recent advances. Neurochem. Res. 21(1996)527-535.

43. Suzuki, M., Sakamoto, Y., Kitamura, K., Fuku-naga, K., Yanamoto, H., Miyamato, E. and Uyemura,K. Phosphorylation of PO glycoprotein in peripheralnerve myelin. J. Neurochem. 55( 1990)1966-1971.

44. Toms, A. D., Fisher, H. R., Goodrum, J. F.,Windes. S. and Morel], P. Metabolism of phosphateand sulphate groups modifying the PO protein of pe-ripheral nervous system myelin. J. Neurochem. 48(1987)883-887.

45. Wiggins, R. C. and Morel!, P. Phosphorylationand glycosylation of myelin proteins in vitro, in sciaticnerve from developing rats. J. Neurochem. 34(1980)627-634.

46. Bruden, K. R. and Podulso, J. F. A phorbol estersensitive kinase catalyses the phosphorylation of POglycoprotein in myelin. J. Neurochem. 46 (1987)1863-1872.

47. Giese, K. P., Martini. R., Lemke, G., Soriano, P.and Schachner. NI. Disruption of the PO gene in miceleads to abnormal expression of recognition moleculesand degeneration of myelin and axons. Cell 71 (1992)565-576.

48. Martini, R., Zielasek, J., Toyka. K. V., Giese. K.P. and Schachner, M. Protein zero(P0)-deficient miceshow myelin degeneration in peripheral nerves charac-teristic of inherited human neuropathies. Nat. Genet.11 (1995)281-286.

49.Jackusch. H.. Nave, K. A., Grenninlogh. G. andSchmitt, J. T. Molecular genetics of nervous and neu-romuscular systems. In: Molecular Biology of the Neuron. Davies, R. W. and Morris, B. J., eds. Oxford Uni-versity Press, 1996, pp. 21-66.

50.Maeda, M. and Narita. M. Affinity of M. lepraewith Lewis rat Schwannoma cell line TC-98. Lep. Rev.58(1987)39.

51..Rees, R. J. W., Weddell, G.. Palmer, G. and Ja-munson, D. G. Experimental studies on nerve fibres inleprosy II. The reaction of human Schwalm cells to-wards carbon particles and leprosy bacilli. hit. .1. Lepr.33(1965)160-175.

52.Chowdhury, A. C., Mistry, N. F. and Antia, N. H.Blocking of M. leprae adherence to disassociatedSchwalm cells by ant itnycobacterial antibodies. Scand.J. Immunol. 30(1989)505-509.

53. Astarie-Dequeker, C., N'Diaye, E. N., LeCabec.V.. Rittig. M. G., Prandi, J. and Maridonneau-Parini, I.The mannose receptor mediates uptake of pathogenicand non-pathogenic mycobacteria and bypasses bacte-ricidal responses in human macrophages. Infect. lmmum 67(1999)469-477.

54. Bermudez, L. E.. Goodman. J. and Petrofsky, M.Role of complement receptors in uptake of M.(whimby macrophages in vivo: evidence from studies usingCD 18-deficient mice. Infect. Immun. 67(1999)4912-4916.

55. Ng. V., Zanazzi. G.. Timpl. R.. Talts, J. F., Salzer,J. L., Brennan, P. J. and Ramhukkana, A. Role of thecell wall phenolic glycol 01d-1 in the peripheral nervepredilection of Mymbacierium leprae. Cell 103 (2000)511-524.

56. Scollard, D. M. Association of Mycobacteriumleprae with human endothelial cells in vitro. Lab. Invest. 80(2000)663-669.

2020 © International Journal of Leprosy and other Mycobacterial Diseases all right reaserved GN1