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Gervois, P.

Publications and source records attributed to Gervois, P..

2 recordsLinked to original sources

Detection of bifidobacterial lipoproteins with anti-viral potential in donor human milk

Background: Group B coxsackieviruses (CVBs) are involved in triggering type 1 diabetes. Free bifidobacterial lipoproteins (BLps) prevent CVBs cell infection. Our objective is to isolate free BLps potentially released by bifidobacteria in breastmilk and document their bioavailability. Methods: Bifidobacterium breve and B. longum were quantified by qPCR in samples donated to the hospitals biobank (DHM) within two weeks following delivery. BLps were captured onto CV B4, analyzed by SDS-PAGE and competitive ELISA. BLps transport through Caco-2 monolayers was monitored after DHM contact. Titration of anti-CV B IgA was carried out by ELISA. Results: Among the 90 enrolled donors, seven were excluded, 68 donated a unique sample and 15 donated multiple specimens (2 to 12). B. breve and B.longum were detected in 93.0 % and 32.8% unique DHM samples, respectively. The two species showed unstable counts in the multiple donation group. Although at highly variable amounts, BLps were readily detected. Free B.longum Lps were found in absence of B.longum itself. The BLps crossed the cell layer within 4h still binding CV B4. Conclusion: DHM contained BLps able to cross a cell layer mimicking the intestine still retaining their capacity to bind CV B. It suggested a possible newborns systemic protection against CV B4 infection that needs further investigation.

microbiology↗

Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation

The ability of immune-modulating biologics to prevent and reverse pathology has transformed recent clinical practice. Full utility in the neuroinflammation space, however, requires identification of both effective targets for local immune-modulation and a delivery system capable of crossing the blood-brain-barrier. The recent identification and characterization of a small population of regulatory T cells (Tregs) resident in the brain presents one such potential therapeutic target. Here we identified brain IL2 levels as a limiting factor for brain-resident Tregs. We developed a gene-delivery approach for astrocytes, with a small-molecule on-switch to allow temporal control, and enhanced production in reactive astrocytes to spatially-direct delivery to inflammatory sites. Mice with brain-specific IL2 delivery were protected from traumatic brain injury, stroke and multiple sclerosis models, without impacting the peripheral immune system. These results validate brain-specific IL2 gene-delivery as effective protection against neuroinflammation, and provide a versatile platform for delivery of diverse biologics to neuroinflammatory patients.

immunology↗