Effect of unique Mycobacterium leprae phenolic glycolipid-I (PSL-I) on tumour necrosis factor production by human mononuclear cells

Mycobacterium leprae cell wall-associated components are found in large amo unts in the tissues of leprosy patients, particularly those at the lepromat ous pole. Among these molecules, the phenolic glycolipid-I (PGL-I), unique to M. leprae, has been involved in the selective anergy observed in the lep romatous patients. Armadillo-derived M. leprae retains only a small proport ion of the total PGL-I found in infected tissues. Therefore, the addition o f 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 prod uction by normal human peripheral blood mononuclear cells (PBMC) and by a h uman monocytic leukaemia cell line (THP-1) following stimulation with kille d M. leprae. PGL-I alone did not induce TNF secretion by PBMC, but when ass ociated with a sub-optimal dose of armadillo-derived M. leprae increased th e release of this cytokine. In agreement with these results, M. leprae-expo sed THP-1 cells did not secrete detectable levels of TNF unless PGL-I was s imultaneously added to the culture, This increase in TNF production suggest s that PGL-I plays a role in the induction of TNF during the natural infect ion. In addition, the modulatory effect of PGL-I on TNF release by THP-1 ce lls reinforces that monocytes are one of the possible targets of this molec ule.