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• W4293222125 abstract "ABSTRACT Leptospira interrogans are pathogenic bacteria responsible for leptospirosis, a worldwide zoonosis. All vertebrates can be infected, and some species like humans are susceptible to the disease whereas rodents such as mice are resistant and become asymptomatic renal carriers. Leptospires are stealth bacteria that are known to escape several immune recognition pathways and resist killing mechanisms. We recently published that leptospires may survive intracellularly and exit macrophages, in part by escaping xenophagy, a pathogen-targeting form of autophagy. Interestingly, autophagy is one of the antimicrobial mechanisms often highjacked by bacteria to evade the host immune response. In this study we therefore explored whether leptospires subvert the key molecular players of autophagy to facilitate the infection. We showed in macrophages that leptospires triggered a specific accumulation of autophagy-adaptor p62 in puncta-like structures, without major alteration of autophagy flux. Unlike active bacterial mechanisms described to date, we demonstrated that leptospires trigger p62 accumulation using a passive mechanism of LPS signaling via TLR4/TLR2. p62 is a central pleiotropic protein, not only involved in autophagy, but also mediating cell stress and death, via the translocation of transcription factors. We demonstrated that Leptospira -driven accumulation of p62 induced the translocation of transcription factor NRF2. However, NRF2 translocation upon Leptospira infection did not result as expected in antioxydant response, but dampened the production of inflammatory mediators such as iNOS/NO, TNF and IL6. Overall, these findings highlight a novel passive bacterial mechanism linked to p62/NRF2 signaling that decreases inflammation and contributes to the stealthiness of leptospires." @default.
• W4293222125 created "2022-08-27" @default.
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• W4293222125 date "2022-08-24" @default.
• W4293222125 modified "2023-10-18" @default.
• W4293222125 title "Leptospiral lipopolysaccharide dampens inflammation through upregulation of autophagy adaptor p62 and NRF2 signaling in macrophages" @default.
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• W4293222125 doi "https://doi.org/10.1101/2022.08.24.505079" @default.
• W4293222125 hasPublicationYear "2022" @default.
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