Down‐Regulatory Effect of Mycobacterium leprae Cell Wall Lipids on Phagocytosis, Oxidative Respiratory Burst and Tumour Cell Killing by Mouse Bone Marrow Derived Macrophages

Abstract

The authors have previously demonstrated that lipids from Mycobacterium leprae cell walls inhibit macrophage functions and are endowed with anti-inflammatory properties in vivo. To investigate these observations further, the authors describe here the influence of dead M. leprae or of the lipids extracted from the cell wall of the mycobacterium, enclosed in liposomes, on the phagocytic, oxidative respiratory burst and tumouricidal ability of bone marrow derived macrophages in vitro. Dead M. leprae or its cell wall lipids abrogated the oxidative respiratory burst and phagocytic ability of mouse bone marrow derived macrophages. A dose-dependent inhibitory effect of the bacterial lipid extract on tumour cell killing by lipopolysaccharide (LPS)-activated bone marrow derived macrophages was demonstrated. However, when delipidated M. leprae was added to cultures of bone marrow derived macrophages, immune phagocytosis and superoxide production was up-regulated. Mycobacterium leprae or its lipids did not appear to be toxic to those cells assayed by the MTT (methyl thiazol tetrazolium) test. These data, added to our preceding observations, support the hypothesis that the down-regulatory activity of M. leprae wall lipids on macrophage function might be one of the evasive mechanisms of the bacterium to enable it to perpetuate itself in the host tissues.

Use of Gene Dosage Effects for a Whole-Genome Screen To Identify Mycobacterium marinum Macrophage Infection Loci

“…Since tuberculosis and other mycobacteria can produce capsule (34,55,75,76,87,93), it is tempting to speculate that these genes are involved in the synthesis of a capsule-like structure during certain stages of infection. However, it is equally likely that modification to the mycobacterial cell wall can modulate phagocytosis similar to the cell wall of M. leprae (70)(71)(72). Since mycobacteria are normally considered intracellular pathogens, the fact that there are stages of mycobacterial infection where the bacteria are primarily found extracellular (26,56,61,99,100) and may be expressing antiphagocytic activities is only rarely examined.…”

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

“…The population of cells in the pleural cavity is exclusively composed of mononuclear cells, more specifically monocytes [16,24,25]. Pleural macrophages have similar phenotypic and morphologic characteristics to alveolar macrophages [30,31], and the pleural space shares the same lymphatic drainage as the respiratory tract.…”

“…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.…”

“…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]. Further, ML reduces BCG-induced inflammation and transforms macrophages in epithelioid cells [13].…”

“…Further, ML reduces BCG-induced inflammation and transforms macrophages in epithelioid cells [13]. Otherwise, delipidated ML (MLD) acquires inflammatory properties, including the ability to activate macrophages [12,13,15,16].…”