Lipids from Mycobacterium leprae cell wall suppress T‐cell activation in vivo and in vitro

Abstract

SUMMARYThe influence of Mycobacterium leprae cell wall lipids on lymphocyte functions has been investigated in vivo (delayed-type hypersensitivity) and in vitro. The inflammatory response has been earlier evaluated by the mouse footpad oedema model and the delipidated mycobacteria evoked a mild but significant inflammatory response. Herein a higher level of hypersensitivity reaction was observed with delipidated bacilli than with the intact mycobacteria. The lipids obtained from the extract of M. leprae external cell wall were used to prepare liposomes, which have not been shown to be toxic to lymphocytes. The method of lipidic extraction and the sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the lipid fraction did not reveal any trace of proteins. Thin-layer chromatography of this extract detected four different bands with an apolar character, suggestive of mycolic and fatty acids. These same M. leprae liposomes potently suppressed lymph node cells, as well CD4+ and CD8+ T-cell lines, and an antigen-specific T-cell clone (T 4-9) proliferation, even under potent stimulus. Cholesterol-choline liposomes, unrelated to M. leprae liposomes, used as a control in the biological assays showed no significant effect on lymphoblastic activity, which points to the specificity of M. leprae lipids. These data demonstrated that M. leprae cell wall lipids induce immune suppression in mice without causing any membrane alteration in T cells as assessed throughout kinetic studies in vitro. This fact is closely related to the down-regulating effect induced by M. leprae lipids which we have previously observed in macrophage functions in vivo and in vitro. Although this lipidic fraction showed a suppressive action on T lymphocytes in vitro (proliferation) and in vivo (delayed-type hypersensitivity), its possible significance in the establishment of a specific immune response to M. leprae must be further investigated.

Mycobacterial Di-O-Acyl-Trehalose Inhibits Mitogen- and Antigen-Induced Proliferation of Murine T Cells In Vitro

“…Thus, the chemical basis of this cross-reactivity between DAT and M. leprae cells is of great interest. For instance, the presence of DAT in M. leprae cells could also account for some immunosuppressive effects reported in LAM-and phenolic glycolipid-free lipid extracts obtained from this species (30).…”

Host-Pathogen Interactions inCampylobacterInfections: the Host Perspective

“…Two of these, with molecular masses of 47 and 84 kDa, were found to elicit strong serum IgG responses in humans following infection, including sera from volunteers who were immune to C. jejuni infection when rechallenged. Capsular polysaccharide antigens, the basis of the Penner serotyping scheme, are also immunogenic, eliciting both type-specific and cross-reactive responses (114,144). The CDT produced by Campylobacter is also immunogenic in human infections, eliciting toxin-neutralizing antibodies (1).…”

Opposite effects of M. leprae or M. bovis BCG delipidation on cellular accumulation into mouse pleural cavity. Distinct accomplishment of mycobacterial lipids in vivo

“…Recently, it has been reported that mycobacterial lipids indirectly inhibit T cell mitogenesis by infected macrophages [5,10,17,18,27]. Phosphatidylserine collaborates with reactive nitrogen intermediates and TGFb, pointing to the essential role of these structures in macrophage function [10,27].…”

“…These liposomes were prepared for the biological assays as a control for LE and for LBCG as previously described [16,17]. Briefly, cholesterol (Sigma) and phosphatidylcholine (Sigma) both at 10 mM in chloroform were mixed in a molar ratio of 2 : 7.…”

“…Since the bacilli have long-lasting growth, these lipids can diffuse freely, disturbing, the structure and function of host cell membranes. Based on these findings, we extracted external mycobacterial apolar lipids, which seem to belong to fatty acids (possibly branched to lipoarabinomannan [5]) in a preliminary biochemical charcterisation by thin layer cromatography and electrophoresis analysis, without detection of peptidolipids [17]. We have shown that ML cell wall lipids seem to inhibit macrophage activation in vivo [12][13][14] and in vitro [16], and were immunosuppressive for T cells in vivo and in vitro [17].…”