In Vivo Activity of Released Cell Wall Lipids ofMycobacterium bovisBacillus Calmette-Guérin Is Due Principally to Trehalose Mycolates

摘要: The hallmark of Mycobacterium-induced pathology is granulomatous inflammation at the site infection. Mycobacterial lipids are potent immunomodulators that contribute to response and released in appreciable quantities by intracellular bacilli. Previously we investigated granulomagenic nature peripheral cell wall Mycobacterium bovis bacillus Calmette-Guerin (BCG) coating onto 90-μm diameter microspheres were mixed into Matrigel matrix with syngeneic bone marrow-derived macrophages injected i.p. mice. These studies demonstrated BCG elicit proinflammatory cytokines recruit leukocytes. In current study determined responsible for this effect. BCG-derived fractionated purified liquid chromatography preparative TLC. isolated fractions including phosphatidylinositol dimannosides, cardiolipin, phosphatidylglycerol, phosphatidylethanolamine, trehalose monomycolate, dimycolate, mycoside B. Trehalose when delivered murine macrophages, induced greatest secretion IL-1β, IL-6, TNF-α vitro. dimycolate similarly these ex vivo matrices over course 12 days. monomycolate also profound neutrophil recruitment vivo. Experiments TLR2 or TLR4 gene-deficient mice revealed no defects responses mycolates, although MyD88-deficient manifested significantly reduced cytokine production. results demonstrate particularly most bioactive extract, inducing a cascade influences granuloma formation.