Mycobacterium tuberculosiscontrols host innate immune activation through cyclopropane modification of a glycolipid effector molecule

• DOI: 10.1084/jem.20041668
• Publication Date: 2005-02-15T01:13:39Z
• Authors: Vivek Rao; Nagatoshi Fujiwara; Steven A. Porcelli; Michael S. Glickman
• Keywords: Proinflammatory cytokine; Pathogenesis

Mycobacterium tuberculosis (Mtb) infection remains a global health crisis. Recent genetic evidence implicates specific cell envelope lipids in Mtb pathogenesis, but it is unclear whether these compounds affect pathogenesis through structural role the wall or as effectors that interact directly with host cells. Here we show cyclopropane modification of glycolipid trehalose dimycolate (TDM) critical for growth during first week mice. In addition, TDM by synthase pcaA was both necessary and sufficient proinflammatory activation macrophages early infection. Purified isolated from cyclopropane-deficient mutant hypoinflammatory induced less severe granulomatous inflammation mice, demonstrating fine structure this to its activity. These results established contained direct identified temporal control immune pathogenic strategy Mtb.