Effect of unique Mycobacterium leprae phenolic glycolipid-I (PGL-I) on tumour necrosis factor production by human mononuclear cells.
Mycobacterium leprae cell wall-associated components are found in large amounts in the tissues of leprosy patients, particularly those at the lepromatous pole. Among these molecules, the phenolic glycolipid-I (PGL-I), unique to M. leprae, has been involved in the selective anergy observed in the lepromatous patients. Armadillo-derived M. leprae retains only a small proportion of the total PGL-I found in infected tissues. Therefore, the addition of PGL-I to M. leprae in vitro is important for a better understanding of M. leprae effects in vivo. We have studied the influence of PGL-I on TNF production by normal human peripheral blood mononuclear cells (PBMC) and by a human monocytic leukaemia cell line (THP-1) following stimulation with killed M. leprae. PGL-I alone did not induce TNF secretion by PBMC, but when associated with a sub-optimal dose of armadillo-derived M. leprae increased the release of this cytokine. In agreement with these results, M. leprae-exposed THP-1 cells did not secrete detectable levels of TNF unless PGL-I was simultaneously added to the culture. This increase in TNF production suggests that PGL-I plays a role in the induction of TNF during the natural infection. In addition, the modulatory effect of PGL-I on TNF release by THP-1 cells reinforces that monocytes are one of the possible targets of this molecule.
Charlab
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Leprosy Laboratory, Oswaldo Cruz Foundation, Av. Brasil, 4365, Manguinhos, CEP 21045-000 Rio de Janeiro, Brazil.
Sarno
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EN
Chatterjee
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Pessolani
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MC
D000942:Antigens, Bacterial / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D006017:Glycolipids / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D009166:Mycobacterium leprae; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000942:Antigens, Bacterial; D006017:Glycolipids; D014409:Tumor Necrosis Factor-alpha; C045169:phenolic glycolipid I, Mycobacterium leprae