Lipids from Mycobacterium leprae cell wall are endowed with an anti‐inflammatory property and inhibit macrophage function in vivo

Abstract

SUMMARYIn general, the majority of bacteria are pro-inflammatory when injected in experimental animals. However, Mycobacterium leprae has no inflammatory effect when injected into mouse footpad, but using the delipidated mycobacteria we observed a mild significant increase in footpad oedema. Other mycobacteria, Mycobacterium bovis-BCG or M. tuberculosis induce a strong paw oedema. Furthermore, M. leprae reduced locally the BCG-induced inflammatory reaction in mouse footpad, whereas delipidated M. leprae did not influence this reaction. Both M. leprae and M. leprae cell wall lipids blocked immune phagocytosis in vivo by inflammatory macrophages (from an induced focus). In contrast delipidated M. leprae stimulated the phagocytosis reaction. Neither intact M. leprae, delipidated M. leprae, nor its lipids had any toxic effect on macrophages or on cell migration. Although M. leprae did not interfere on cell influx and cell type in an induced-inflammatory site, this mycobacterium led to the appearance of a distinct cell population in vivo. The hypothesis is that M. leprae would transform macrophages in epithelioid cells, suggested by morphology analysis of cells by fluorescence-activated cell sorter and observed under optic microscopy.

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.…”

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

“…CD 151, WHO). Based on previous results in the literature [1,2,[12][13][14], the number of bacteria used in all assays was 8 × 10 6 bacilli.…”

“…Mycobacterium leprae (ML) was delipidated (MLD) by treatment of the bacterium with petroleum ether (Merck, Darmstadt, Germany 60ЊC b.p.) as previously described [13,24]. With this procedure, neutral lipids are extracted from the cell wall and do not alter the basic morphology of the bacterium as analyzed by optical microscopy.…”

“…This might be either because the bacterium is devoid of pro-inflammatory mediators, or because it down-regulates the inflammatory response. In order to test these hypotheses, we have recently demonstrated that M. leprae is endowed with anti-inflammatory properties mediated by the cell wall lipids of the bacterium [12,13]. This effect was demonstrated considering that, contrary to what happens to M. bovis -BCG [2] -delipidated dead M. leprae induces an increased inflammatory response when injected in the foot pad of mice [13].…”

“…In order to test these hypotheses, we have recently demonstrated that M. leprae is endowed with anti-inflammatory properties mediated by the cell wall lipids of the bacterium [12,13]. This effect was demonstrated considering that, contrary to what happens to M. bovis -BCG [2] -delipidated dead M. leprae induces an increased inflammatory response when injected in the foot pad of mice [13]. Yet the inflammatory response induced by BCG is markedly reduced when the bacterium is injected in a site previously injected with dead M. leprae.…”