Leishmania RNA virus exacerbates Leishmaniasis by subverting innate immunity via TLR3-mediated NLRP3 inflammasome inhibition
RVH de Carvalho, DS Lima-Junior… - Nature …, 2019 - nature.com
Leishmania RNA virus (LRV) is an important virulence factor associated with the
development of mucocutaneous Leishmaniasis, a severe form of the disease. LRV-mediated
disease exacerbation relies on TLR3 activation, but downstream mechanisms remain
largely unexplored. Here, we combine human and mouse data to demonstrate that LRV
triggers TLR3 and TRIF to induce type I IFN production, which induces autophagy. This
process results in ATG5-mediated degradation of NLRP3 and ASC, thereby limiting NLRP3 …
development of mucocutaneous Leishmaniasis, a severe form of the disease. LRV-mediated
disease exacerbation relies on TLR3 activation, but downstream mechanisms remain
largely unexplored. Here, we combine human and mouse data to demonstrate that LRV
triggers TLR3 and TRIF to induce type I IFN production, which induces autophagy. This
process results in ATG5-mediated degradation of NLRP3 and ASC, thereby limiting NLRP3 …
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