ORCID Profile
0000-0002-4491-1063
Current Organisations
Institut Pasteur
,
Université Paris Diderot
,
Université Paris Descartes
,
Université Paris Cité
,
INSERM
,
Hôpital universitaire Necker-Enfants malades
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Publisher: Informa UK Limited
Date: 02-2017
DOI: 10.1080/09273948.2016.1276788
Abstract: Describe patient characteristics, treatment, and vision outcomes of Listeria monocytogenes endophthalmitis, an exceedingly rare form of listeriosis. L. monocytogenes endophthalmitis cases in human adults, located through Medline (32) and from disease surveillance centers (11). L. monocytogenes conjunctivitis and keratitis were excluded. Most cases occurred in 2000-2015 (22/43), and almost all in Europe or North America (40/43). Patients were a median 61 years, 57% male (24/42) and half were immunosuppressed. Median days from entering care to diagnosis was 8 (IQR = 5-17). Only four were exogenous infections. L. monocytogenes was identified in 31/35 of anterior eye fluid s les (89%). Antibiotic regimens varied markedly (mostly ≥3 drugs). At diagnosis, most were blind in the affected eye (85%, 28/33), only a third regained normal vision (12/36). Older patients had poorer outcomes. Cases increased over time. Diagnostic delays were common and visual impairment often refractory to treatment, especially in older adults. The condition's rarity and variation in treatment makes it difficult to identify optimum therapy.
Publisher: Frontiers Media SA
Date: 26-03-2019
Publisher: Cold Spring Harbor Laboratory
Date: 20-12-2020
DOI: 10.1101/2020.12.18.423387
Abstract: Retracing microbial emergence and spread is essential to understanding the evolution and dynamics of pathogens. The bacterial foodborne pathogen Listeria monocytogenes clonal complex 1 ( Lm -CC1) is the most prevalent clonal group associated with listeriosis, and is strongly associated with cattle and dairy products. Here we analysed 2,021 Lm -CC1 isolates collected from 40 countries, since the first Lm isolation to the present day, to define its evolutionary history and population dynamics. Our results suggest that Lm -CC1 spread worldwide from North America following the Industrial Revolution through two waves of expansion, coinciding with the transatlantic livestock trade in the second half of the 19 th century and the rapid growth of cattle farming in the 20 th century. Lm -CC1 then firmly established at a local level, with limited inter-country spread. This study provides an unprecedented insight into Lm -CC1 phylogeography and dynamics and can contribute to effective disease surveillance to reduce the burden of listeriosis.
Publisher: Informa UK Limited
Date: 2017
DOI: 10.1038/EMI.2017.15
Publisher: Springer Science and Business Media LLC
Date: 11-12-2017
DOI: 10.1038/S41593-017-0038-4
Abstract: Accumulating evidence support a causal link between Zika virus (ZIKV) infection during gestation and congenital microcephaly. However, the mechanism of ZIKV-associated microcephaly remains unclear. We combined analyses of ZIKV-infected human fetuses, cultured human neural stem cells and mouse embryos to understand how ZIKV induces microcephaly. We show that ZIKV triggers endoplasmic reticulum stress and unfolded protein response in the cerebral cortex of infected postmortem human fetuses as well as in cultured human neural stem cells. After intracerebral and intraplacental inoculation of ZIKV in mouse embryos, we show that it triggers endoplasmic reticulum stress in embryonic brains in vivo. This perturbs a physiological unfolded protein response within cortical progenitors that controls neurogenesis. Thus, ZIKV-infected progenitors generate fewer projection neurons that eventually settle in the cerebral cortex, whereupon sustained endoplasmic reticulum stress leads to apoptosis. Furthermore, we demonstrate that administration of pharmacological inhibitors of unfolded protein response counteracts these pathophysiological mechanisms and prevents microcephaly in ZIKV-infected mouse embryos. Such defects are specific to ZIKV, as they are not observed upon intraplacental injection of other related flaviviruses in mice.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 03-12-2021
Abstract: Analyses of ~2000 genomes of Listeria monocytogenes main clinical clone reveal its global spread and dynamics.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 16-12-2022
DOI: 10.1126/SCIIMMUNOL.ABQ2061
Abstract: Emergency hematopoiesis is a concerted response aimed toward enhanced protection from infection, involving multiple cell types and developmental stages across the immune system. Despite its importance, the underlying molecular regulation remains poorly understood. The deubiquitinase USP22 regulates the levels of monoubiquitinated histone H2B (H2Bub1), which is associated with activation of interferon responses upon viral infection. Here, we show that in the absence of infection or inflammation, mice lacking Usp22 in all hematopoietic cells display profound systemic emergency hematopoiesis, evident by increased hematopoietic stem cell proliferation, myeloid bias, and extramedullary hematopoiesis. Functionally, loss of Usp22 results in elevated phagocytosis by neutrophilic granulocytes and enhanced innate protection against Listeria monocytogenes infection. At the molecular level, we found this state of emergency hematopoiesis associated with transcriptional signatures of myeloid priming, enhanced mitochondrial respiration, and innate and adaptive immunity and inflammation. Augmented expression of many inflammatory genes was linked to elevated locus-specific H2Bub1 levels. Collectively, these results demonstrate the existence of a tunable epigenetic state that promotes systemic emergency hematopoiesis in a cell-autonomous manner to enhance innate protection, identifying potential paths toward immune enhancement.
Publisher: Informa UK Limited
Date: 02-01-2016
Publisher: Public Library of Science (PLoS)
Date: 21-11-2007
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.TRANSPROCEED.2013.01.082
Abstract: Maribavir (MBV), a UL97 inhibitor, shows good oral bioavailability, low host cell toxicity, and theoretical benefits to inhibit cross-resistant viruses. We herein examined clinical and virological outcomes of 12 patients, including 3 bone marrow recipients and 9 organ recipients infected with resistant cytomegalovirus (CMV) and treated with MBV during 2011-2012. All received at least 800-mg daily doses. They had developed clinical (12/12) and/or virological (11/12) resistance to CMV infection. Based on a decrease of viral load in blood >1.5 log copies/mL half of them responded to MBV treatment. The in idual changes varied from a rapid decrease in viral load (n = 4) to no response (n = 3) with some late response slowly decreasing viremia (n = 3). In 2 cases MBV was used as secondary prophylaxis. No clear parameter emerged as a clinical surrogate for nonresponse to MBV. These results contrast with the lack of efficacy in phase III trials of MBV prophylaxis among stem cell recipients, which were possibly due to low doses or inadequate timing of drug initiation in the study. Additional clinical and surrogate laboratory markers are needed to determine antiviral responses to guide MBV use. Dosage ranging studies might benefit future MBV use.
No related grants have been discovered for Marc Lecuit.