02345nas a2200385 4500000000100000008004100001260001300042653001200055653001100067653002100078653001200099653000900111653001500120653002700135653002500162653001500187653001500202653002400217653002500241653001700266100001500283700001300298700001300311700001600324700000900340700001200349700001600361700001200377245013400389856007800523300001200601490000800613520132400621022001401945 2009 d c2009 Jun10aAnimals10aHumans10aImmunity, Innate10aleprosy10aMice10aMice, Nude10aMicrofilament Proteins10aMycobacterium leprae10aNF-kappa B10aPhagosomes10aSignal Transduction10aToll-Like Receptor 210aTransfection1 aTanigawa K1 aSuzuki K1 aKimura H1 aTakeshita F1 aWu H1 aAkama T1 aKawashima A1 aIshii N00aTryptophan aspartate-containing coat protein (CORO1A) suppresses Toll-like receptor signalling in Mycobacterium leprae infection. uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2691979/pdf/cei0156-0495.pdf a495-5010 v1563 a

Mycobacterium leprae is an intracellular pathogen that survives within the phagosome of host macrophages. Several host factors are involved in producing tolerance, while others are responsible for killing the mycobacterium. Tryptophan aspartate-containing coat protein (TACO; also known as CORO1A or coronin-1) inhibits the phagosome maturation that allows intracellular parasitization. In addition, the Toll-like receptor (TLR) activates the innate immune response. Both CORO1A and TLR-2 co-localize on the phagosomal membrane in the dermal lesions of patients with lepromatous leprosy. Therefore, we hypothesized that CORO1A and TLR-2 might interact functionally. This hypothesis was tested by investigating the effect of CORO1A in TLR-2-mediated signalling and, inversely, the effect of TLR-2-mediated signalling on CORO1A expression. We found that CORO1A suppresses TLR-mediated signal activation in human macrophages, and that TLR2-mediated activation of the innate immune response resulted in suppression of CORO1A expression. However, M. leprae infection inhibited the TLR-2-mediated CORO1A suppression and nuclear factor-kappaB activation. These results suggest that the balance between TLR-2-mediated signalling and CORO1A expression will be key in determining the fate of M. leprae following infection.

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