Effect of Mycobacterium leprae lipids on BCG- and carrageenan-induced cellular recruitment in mouse pleurisy.

Pathogenic mycobacteria survive inside macrophages and deactivate these cells, using a mechanism that is still poorly understood. Mycobacterial cell wall lipids constitute the first contact with the host cell. Although Mycobaterium leprae and M. bovis BCG share common antigens, they induce opposite inflammatory responses. Apolar M. leprae lipids have been shown to be anti-inflammatory by down-regulating macrophage activation and T-cell functions. We wonder if these lipids would influence cellular migration to BCG or to other inflammatory agent. We investigated the effect of M. leprae, its lipids or delipidated bacteria on acute and chronic BCG- or carrageenan-induced pleurisy. Previous injection of intact or delipidated M. leprae did not alter either the BCG- or carrageenan-induced pleural inflammatory reaction. However, M. leprae lipids enhanced carrageenan-induced acute cellular migration without impairing BCG inflow; moreover, they reduced BCG chronic response. Together these data suggest distinct mechanisms for intracellular deactivation and pleural cell recruitment exerted by mycobacterial structures.

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

OBJECTIVES AND DESIGN: The effect of mycobacterial lipids on the onset of the early acute inflammatory response in BALB/c mice pleurisy was investigated. MATERIALS AND METHODS: Intact Mycobacterium leprae and Mycobacterium bovis BCG (BCG), their lipids, and delipidated mycobacteria were used to evaluate total leukocytes and cell types migrated to the pleural cavity (8 animals/experimental group). RESULTS: BCG Moreau (x10(-6)/cavity), delipidated BCG and its lipids gradually recruited cells leading to arrival, respectively, of neutrophils (7.8+/-1.9, 4.7+/-0.9, 1.8+/-0.25) followed by mononuclear cells (4.8+/-0.8, 3.7+/-0.7, 2.45+/-0.22) and eosinophils (0.39+/-0.08, 0.32+/-0.11, 0.41+/-0.65). BCG delipidation decreased the number of migrated total leukocytes (ANOVA, and Newman-Keuls-Student-test), whereas M. leprae delipidation accumulated neutrophils (0.85+/-0.01) and eosinophils (1.65+/-0.18). CONCLUSIONS: Intact M. leprae and its lipids did not incite any cell recruitment. Apolar external cell wall lipids from M. leprae and BCG induce different cellular responses. They seem to have a crucial importance at the first contact of mycobacteria with the host cell, modulating the influx of neutrophils/macrophages in the early (4/24 h) onset of the inflammatory reaction.

Opposite cellular accumulation and nitric oxide production in vivo after pleural immunization with M. leprae or M. bovis BCG.

Mycobacteria as intracellular pathogens have evolved mechanisms to survive within macrophages. Our previous data showed that M. leprae (ML), unlike M. bovis BCG, did not induce an inflammatory response in the mice subcutaneous tissue. Further, ML inhibited BCG-induced foot pad oedema and seemed to transform macrophages in epithelioid cells. Since these mycobacteria share common antigens, here we seeked to compare the acute and chronic cellular response evoked by ML and BCG in pleurisy of a mycobacteria-susceptible mice (BALB/c). The total leukocytes, the cell type that migrated to the pleural cavity and macrophage activation assayed by nitric oxide release were determined. Live or dead BCG Moreau recruited the same extent of cells, essentially monocytes and neutrophils, dose-dependently, in both acute and chronic pleurisy. BCG-induced eosinophilia was observed only in the acute response (after 24 h of injection). A significant nitric oxide release by pleural macrophages was triggered by BCG Moreau without previous activation. Nevertheless, ML failed to recruit leukocytes to the pleural space or to lead to nitric oxide production despite the number of bacilli used and the time studied (1, 7 or 14 days after injection). Although these mycobacteria have common antigens that cross-react, these data show a distinct ability of ML or BCG to recruit cells to the pleural space and to activate pleural macrophage for nitric oxide production in vivo.