Dysregulated response to mycobacterial cord factor trehalose-6,6′-dimycolate in CD1D-/- mice

The biologic effects of the mycobacterial glycolipid trehalose-6,6′-dimycolate (TDM) include granuloma formation and macrophage activation and are dependent on physical conformation. In mice, the group II CD1 surface molecule CD1d has been implicated in glycolipid presentation. The importance of CD1d interactions in pathology has yet to be established. We hypothesized that mice lacking CD1d (CD1D-/-) would demonstrate dysregulated granulomatous response to TDM, compared with CD1D+/- heterozygous controls. Mice were intravenously injected with TDM-coated polystyrene-divinylbenzene beads and examined for histologic response and for changes in inflammatory cytokine and chemokine mRNA. Control CD1D heterozygous mice demonstrated a granulomatous response, which peaked at day 5. Increased mRNA for tumor necrosis factor-α (TNF-α) and macrophage inflammatory protein-1α (MIP-1α) correlated with development of granulomas, with very little change in interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-...