Tryptophan aspartate-containing coat protein (CORO1A) suppresses Toll-like receptor signalling in Mycobacterium leprae infection.
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.
Department of Bioregulation, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo, Japan.
K
K
Tanigawa
K
K
Suzuki
H
H
Kimura
F
F
Takeshita
H
H
Wu
T
T
Akama
A
A
Kawashima
N
N
Ishii
D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D007918:Leprosy / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D010588:Phagosomes / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D014162:Transfection
D008840:Microfilament Proteins; D016328:NF-kappa B; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C072061:coronin proteins