Biology subjects

Parizot, C.

Publications and source records attributed to Parizot, C..

4 recordsLinked to original sources

bioRxiv2026

Functional Immuno-metagenomics Seizes the Alteration of Microbiota-Immune Interactions at the Early Onset of Multiple Sclerosis

Aberrant health states are characterized by an alteration in microbial composition. Gut microbiota shapes the immune response and potential abnormal host-microbiota interactions warrant inclusion into the framework for identifying a distorted microbiota. Here, we decipher the host surveillance system based on IgA-microbe interactions and leverage it to develop the species Immunomodulatory score (IMscore) to assess immunological imprint based on species IgA opsonisation, abundance and prevalence. We demonstrate its advantage in depicting core immunologically active gut microbiota composed of known and yet-to-be-characterized species across three independent cohorts. We then aggregated IMscores into a global Immunologically active Gut microbiota index (IMGindex) to quantify symbiotic or aberrant microbe-immune interactions at whole community level. We demonstrate IMGindex robustness in depicting altered microbe-immune crosstalk at the early onset of Multiple Sclerosis. Our proof-of-concept study demonstrates the importance of monitoring antibody vigilance over enteric microbes for personalised assessment of gut microbiota health. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=180 SRC="FIGDIR/small/699307v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@1beec85org.highwire.dtl.DTLVardef@19a2b54org.highwire.dtl.DTLVardef@929cb8org.highwire.dtl.DTLVardef@16f29aa_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights and eTOC blurbHighlights 1) IMscore measures immunological imprint of known and uncharacterized species 2) IMscore highlights a core immunologically active gut microbiota 3) IMscore is translated into a community level IMGindex to measure microbiome health 4) IMGindex identifies aberrant microbe-immune responses at the early onset of MS eTOC blurb Nthuku et al. developed an approach to measure a distorted gut microbiota based on the antibody surveillance system over enteric microbes. An immunological imprint for each known and yet-to-be-characterised microbe was assessed and, then, transformed into a global community index for personal monitoring of gut dysbiosis.

microbiology↗

bioRxiv2020

In-depth proteomic analysis of Plasmodium berghei sporozoites using trapped ion mobility spectrometry with parallel accumulation-serial fragmentation

Malaria is caused by Plasmodium spp. protozoan parasites, which are transmitted by female anopheline mosquitoes in the form of sporozoites. Once deposited in the dermis during the blood meal of the mosquito, sporozoites rapidly migrate to the liver for an initial and obligatory round of replication inside hepatocytes, before exponential multiplication of the parasite in the blood and onset of the malaria disease. Sporozoites and liver stages provide attractive targets for the development of a malaria vaccine. Until now, a single antigen from Plasmodium falciparum, the deadliest species infecting humans, has been considered for subunit vaccine clinical development, with limited success so far. This emphazises the need to identify novel targets. In this context, defining the parasite proteome is important not only to guide the down-selection of potential candidate antigens, but also to allow a better understanding of the parasite biology. Previous studies have determined the total proteome of sporozoite stages from the two main human malaria parasites, P. falciparum and P. vivax, as well as P. yoelii, a parasite that infects rodents. Another murine malaria parasite, P. berghei, has been widely used to investigate the biology of Plasmodium pre-erythrocytic stages. However, a deep view of the proteome of P. berghei sporozoites is still missing. To fill this gap, we took advantage of a novel highly sensitive timsTOF PRO mass spectrometer, based on trapped ion mobility spectrometry with parallel accumulation-serial fragmentation. Combined with three alternative methods for sporozoite purification, this approach allowed us to identify the deep proteome of P. berghei sporozoites using low numbers of parasites. This study provides a reference proteome for P. berghei sporozoites, identifying a core set of proteins expressed accross species, and illustrates how the unprecedented sensitivity of the timsTOF PRO system enables deep proteomic analysis from limited sample amounts.

microbiology↗

bioRxiv2020

LOX-1+ immature neutrophils predict severe COVID-19 patients at risk of thrombotic complications

RationalLymphopenia and neutrophil/lymphocyte ratio may have prognostic value in coronavirus disease 2019 (COVID-19) severity. ObjectiveWe sought to investigate the representation of neutrophil subsets in severe and critical COVID-19 patients based on Intensive Care Units (ICU) and non-ICU admission. MethodsWe developed a multi-parametric neutrophil profiling strategy based on known neutrophil markers to distinguish COVID-19 phenotypes in critical and severe patients. ResultsOur results showed that 80% of ICU patients develop strong myelemia with CD10-CD64+ immature neutrophils. Cellular profiling revealed two distinct neutrophil subsets expressing either the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) or the Interleukin-3 receptor alpha (CD123), both significantly overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1-expressing immature neutrophils positively correlated with clinical severity, with the cytokine storm (IL-1{beta}, IL-6, IL-8, TNF), and with intravascular coagulation. Importantly, high proportions of LOX-1+-immature neutrophils are associated with high risks of severe thrombosis. ConclusionsTogether these data suggest that point of care enumeration of LOX-1-immature neutrophils might help distinguish patients at risk of thrombosis complication and most likely to benefit from intensified anticoagulant therapy.

immunology↗

bioRxiv2019

Identification Of Peptides Interfering The LRRK2/PP1 Interaction

Serine/threonine phosphatases are responsible for counteracting the effect of the protein kinases implicated in the development of several pathologies. Here we identified by PEP-scan approach the sequence of a fragment of LRRK2, a Parkinsons disease associated protein, interacting with the phosphatase PP1. The fragment, that is located in a LRRK2 domain of undefined function, was associated in N-terminal to an optimized cell penetrating peptide in order to study their in vitro and in vivo biological activity. From this original sequence, we developed and studied five interfering peptides (IPs) and identified two peptides able to disrupt the LRRK2/PP1 interaction by in vitro competition in anti-LRRK2 immunoprecipitates. Using FITC-labelled peptides, we confirmed the internalization of the peptides in cell lines as well as in and primary human normal and pathological cells. Finally, we have confirmed by ELISA test the association of Mut3DPT-LRRK2-Long and Mut3DPT-LRRK2-Short peptides to purified PP1 protein in a selective manner. The shortest peptides, MuteDPT-LRRK2-5 to 8 with either N or C-terminal deletions are not able neither disrupt the association LRRK2/PP1 nor to associate to purified PP1 protein. The peptides Mut3DPT-LRRK2-Long and Mut3DPT-LRRK2-Short may be new tools to study the role of LRRK2/PP1 interaction in normal and pathological conditions.

molecular biology↗