Lipoarabinomannans (LAMs) are glycolipids from the mycobacterial cell wall that exhibit various biological activities, including proinflammatory and anti-inflammatory responses. However, little is known about the properties of lipomannans (LMs), considered to be precursors of LAMs. In this study, we provide evidence that LMs purified from Mycobacterium chelonae and a clinical strain of Mycobacterium kansasii stimulated mRNA expression and secretion of @entity310 and @entity687 from @entity1 macrophage-like differentiated THP-1 cells. In contrast to LMs, LAMs were not able to induce a significant cytokine-inducing effect. The mechanism of activation by LMs was investigated using various Abs raised against surface receptors for multiple bacterial products. The presence of anti- @entity5750 or @entity2938 ( @entity2938 ) Abs profoundly affected production of @entity310 and @entity687 , suggesting that both @entity5750 and @entity2938 participate in the LM-mediated activation process. Furthermore, stimulation of cells was dependent on the presence of the @entity5752 , a plasma protein that transfers glycolipids to @entity5750 . Chemical degradation of the arabinan domain of mannose-capped LAM from M. kansasii, which presented no cytokine-eliciting effect, restored the cytokine-inducing activity at a level similar to those of LMs. These results support the hypothesis that the presence of an arabinan in LAMs prevents the interaction of these glycolipids with @entity2938 / @entity5750 receptors. In addition, we found that phosphatidylinositol dimannosides isolated from M. kansasii did not induce cytokine secretion. This study suggests that LMs isolated from different mycobacterial species participate in the immunomodulation of the infected host and that the D-mannan core of this glycolipid is essential for this function.

Lipomannans, but not lipoarabinomannans, purified from Mycobacterium chelonae and Mycobacterium kansasii induce @entity310 and XXXX secretion by a @entity5750 -toll-like receptor 2-dependent mechanism.

@entity1 :: ('9606', 'Species') :: ['human'] @entity5752 :: ('3929', 'Gene') :: ['LPS-binding protein'] @entity5750 :: ('929', 'Gene') :: ['CD14'] @entity310 :: ('7124', 'Gene') :: ['TNF-alpha'] @entity2938 :: ('7097', 'Gene') :: ['TLR2', 'anti-Toll-like receptor 2'] @entity687 :: ('3576', 'Gene') :: ['IL-8']
@entity687 :: (3576,Gene) :: ['IL-8']
