Dead Mycobacterium leprae inhibits phagocytosis by inflammatory macrophages in vivo. Participation of the bacteria cell lipids in the phenomenon

Moura, A C N; Mariano, Mário

doi:10.1590/s0074-02761990000300020

Cited by 8 publications

(13 citation statements)

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“…ML possesses anti-inflammatory properties since it could reduce this BCG-induced response in vivo. As we have previously shown 8 dead ML when injected in mice blocks phagocytosis by inflammatory macrophages.…”

Section: Introductionsupporting

confidence: 56%

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

Moura

Mariano

1996

Immunology

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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.

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Section: Introductionsupporting

confidence: 56%

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

Moura

Mariano

1996

Immunology

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“…Yet results obtained with the Trypan Blue exclusion technique and the MTT metabolic assays exclude a possible toxic effect of LE on macrophages. The observation that the inhibitory activity of LE in vitro is in the same range of potency as that obtained in vivo [12,13] suggests a direct effect of LE on macrophage functions in both experimental conditions. The fact that delipidated bacilli stimulated macrophage functions when added to BMD macrophage cultures, also correlates with data obtained in vivo [12,13].…”

Section: Macrophage Deactivation Induced By Mycobacterium Leprae Lipimentioning

confidence: 52%

“…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.…”

Section: Methodsmentioning

confidence: 99%

“…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].…”

Section: Introductionmentioning

confidence: 99%

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

1997

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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.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2008

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We recently identified two loci, mel1 and mel2, that affect macrophage infection by Mycobacterium marinum. The ability of these loci to confer enhanced infection in trans is presumably due to gene dosage effects since their presence on plasmids increases expression from five-to eightfold. Reasoning that this phenomenon would allow identification of other mycobacterial genes involved in macrophage infection, we conducted a screen of an M. marinum DNA library that provides 2.6-fold coverage of the entire genome for clones that affect macrophage infection. Our preliminary screen identified 76 plasmids that carry loci affecting macrophage infection. We eliminated plasmids that do not confer the expected phenotype when retransformed (70%), that have identical physical maps (5%), or that carry either of the mel1 or mel2 loci (14%) from further consideration. Four loci that confer enhanced infection (mel) and four that confer repressed infection (mrl) of macrophages were identified, and two of each group were chosen for detailed analysis. Saturating transposon mutagenesis was used to identify the loci responsible, and M. marinum mutants were constructed in the genes involved. We expect these genes to provide insight into how mycobacteria parasitize macrophages, an important component of innate immunity.Mycobacterium marinum is a natural pathogen of humans (41, 49, 57), fish, and amphibians (18), causing more than 150 human infections each year in the United States alone (29). Although M. marinum causes primarily skin lesions on the extremities in humans (19), it causes a systemic tuberculous disease in fish and amphibians (30,73,101). M. marinum infections result in granuloma formation, whether in humans, mice, fish, or amphibians (18)(19)(20)101). Granuloma formation occurs because macrophages become infected and allow growth of M. marinum during disease (19, 74) and in laboratory model systems (7,33,69,81). These characteristics of infections, along with the relative ease of manipulation (3,37,82,88), rapid growth rate compared to other pathogenic mycobacteria (18), and the presence of numerous useful virulence models (11,20,27,33,84,89,92), have aroused great interest in the molecular mechanisms of M. marinum pathogenesis. Significant progress has been made toward understanding M. marinum evolution (106), trafficking (7,86,98), secretion (1, 36), gene regulation (6, 82), photochromogenicity (35, 83), cell wall synthesis (3, 24, 37), granuloma formation (23, 27, 97), resistance to oxidative species (78,79,95,96), and mechanisms of macrophage infection (32, 38, 66).As a means to better understand the molecular mechanisms of macrophage infection by M. marinum, we recently screened a genomic library for loci that have the ability to confer enhanced macrophage infection to M. smegmatis (32), a nonpathogenic mycobacterial species that does not infect macrophages efficiently. We identified two M. marinum loci, mel1 and mel2, that confer enhanced macrophage infection to both M. smegmatis and M. marinum. The phenotypic effec...

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Dead Mycobacterium leprae inhibits phagocytosis by inflammatory macrophages in vivo. Participation of the bacteria cell lipids in the phenomenon

Cited by 8 publications

References 0 publications

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

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

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

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

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