François Trottein's research while affiliated with Université de Lille and other places

Publications (236)

Article
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Obese patientss with nonalcoholic steatohepatitis (NASH) are particularly prone to developing severe forms of coronavirus disease 19 (COVID-19). The gut-to-lung axis is critical during viral infections of the respiratory tract, and a change in the gut microbiota's composition might have a critical role in disease severity. Here, we investigated the...
Article
Full-text available
Obese patients with non-alcoholic steatohepatitis (NASH) are prone to severe forms of COVID-19. There is an urgent need for new treatments that lower the severity of COVID-19 in this vulnerable population. To better replicate the human context, we set up a diet-induced model of obesity associated with dyslipidemia and NASH in the golden hamster (kn...
Article
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The development of anti-infectives against a large range of AB-like toxin-producing bacteria includes the identification of compounds disrupting toxin transport through both the endolysosomal and retrograde pathways. Here, we performed a high-throughput screening of compounds blocking Rac1 proteasomal degradation triggered by the Cytotoxic Necrotiz...
Article
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Non-conventional T cells, such as γδ T and invariant natural killer T (iNKT) cells, are emerging players in fighting cancer. Alpha-galactosylceramide (α-GalCer) is used as an exogenous ligand to activate iNKT cells. Human cells don’t have a direct pathway producing α-GalCer, which, however, can be produced by bacteria. We searched the literature fo...
Article
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Drug repurposing has the advantage of shortening regulatory preclinical development steps. Here, we screened a library of drug compounds, already registered in one or several geographical areas, to identify those exhibiting antiviral activity against SARS-CoV-2 with relevant potency. Of the 1,942 compounds tested, 21 exhibited a substantial antivir...
Article
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The expanding knowledge on the systemic influence of the human microbiome suggests that fecal samples are underexploited sources of new beneficial strains for extra-intestinal health. We have recently shown that acetate, a main circulating microbiota-derived molecule, reduces the deleterious effects of pulmonary Streptococcus pneumoniae and enteric...
Preprint
Inflammation is a complex physiological process triggered in response to harmful stimuli. It involves specialized cells of the immune system able to clear sources of cell injury and damaged tissues to promote repair. Excessive inflammation can occur as a result of infections and is a hallmark of several diseases. The molecular basis underlying infl...
Article
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Short-chain fatty acids (SCFAs) are metabolites produced mainly by the gut microbiota with a known role in immune regulation. Acetate, the major SCFA, is described to disseminate to distal organs such as lungs where it can arm sentinel cells, including alveolar macrophages, to fight against bacterial intruders. In the current study, we explored mec...
Article
Mounting evidence suggests that the gut-to-lung axis is critical during respiratory viral infections. We herein hypothesized that disruption of gut homeostasis during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may associate with early disease outcomes. To address this question, we took advantage of the Syrian hamster mod...
Article
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The SARS-CoV-2 outbreak has highlighted the need for broad-spectrum antivirals against coronaviruses (CoVs). Here, pheophorbide a (Pba) was identified as a highly active antiviral molecule against HCoV-229E after bioguided fractionation of plant extracts. The antiviral activity of Pba was subsequently shown for SARS-CoV-2 and MERS-CoV, and its mech...
Preprint
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Neuroinvasion by SARS-CoV-2 is now accepted. To investigate whether low testosterone levels observed in men with severe COVID-19 could be of central origin, we retrospectively analyzed blood samples from 60 male intensive-care patients and explored SARS-CoV-2 brain entry using animal and cellular models as well as adult COVID-19 patient and fetal h...
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Coronavirus disease 2019 (COVID-19) can damage cerebral small vessels and cause neurological symptoms. Here we describe structural changes in cerebral small vessels of patients with COVID-19 and elucidate potential mechanisms underlying the vascular pathology. In brains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected indivi...
Preprint
A challenge for the development of host-targeted anti-infectives against a large spectrum of AB-like toxin-producing bacteria encompasses the identification of chemical compounds corrupting toxin transport through both endolysosomal and retrograde pathways. Here, we performed a high-throughput screening of small chemical compounds blocking active R...
Article
Full-text available
Gut interleukin-17A (IL-17)-producing γδ T cells are tissue-resident cells that are involved in both host defense and regulation of intestinal inflammation. However, factors that regulate their functions are poorly understood. In this study, we find that the gut microbiota represses IL-17 production by cecal γδ T cells. Treatment with vancomycin, a...
Preprint
Drug repurposing has the advantage of shortening regulatory preclinical development steps. Here, we screened a library of drug compounds, already registered in one or several geographical areas, to identify those exhibiting antiviral activity against SARS-CoV-2 with relevant potency. Of the 1,942 compounds tested, 21 exhibited a substantial antivir...
Article
Full-text available
Short-chain fatty acids (SCFAs) are the main metabolites produced by the gut microbiota via the fermentation of complex carbohydrates and fibers. Evidence suggests that SCFAs play a role in the control of infections both through direct action on microorganisms and on host signaling. This review summarizes the main microbicidal effects of SCFAs and...
Article
Introduction La BPCO est une pathologie inflammatoire chronique pulmonaire qui peut être exacerbée par des virus, comme le virus respiratoire syncitial (VRS) ou le virus de la grippe. Les cytokines IL-20 dont la sécrétion est induite dans l’épithélium respiratoire après infection virale, interviennent dans les mécanismes de défense anti-infectieuse...
Article
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Along with respiratory tract disease per se, viral respiratory infections can also cause extrapulmonary complications with a potentially critical impact on health. In the present study, we used an experimental model of influenza A virus (IAV) infection to investigate the nature and outcome of the associated gut disorders. In IAV-infected mice, the...
Article
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Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. The major bacterial cause of COPD exacerbations is non-typeable Haemophilus influenzae (NTHi). 25 to over 80% of cases are associated with NTHi. This susceptibility to infection involves a defective production of interleukin (IL)-22 which plays an im...
Article
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The current pandemic of coronavirus disease (COVID) 2019 constitutes a global public health issue. Regarding the emerging importance of the gut-lung axis in viral respiratory infections, analysis of the gut microbiota’s composition and functional activity during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might be instr...
Article
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Bacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host’s defense against viral respiratory infections. The gut microbiota’s composition and function can be profoundly affected in many disease settings, including acute infections, and these changes...
Article
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CD1d-restricted invariant Natural Killer T (iNKT) cells represent a unique class of T lymphocytes endowed with potent regulatory and effector immune functions. Although these functions are acquired during thymic ontogeny, the sequence of events that gives rise to discrete effector subsets remains unclear. Using an unbiased single-cell transcriptomi...
Article
CD1d-restricted invariant Natural Killer T (iNKT) cells represent a unique class of T lymphocytes endowed with potent regulatory and effector immune functions. Although these functions are acquired during thymic ontogeny, the sequence of events that gives rise to discrete effector subsets remains unclear. Using an unbiased single-cell transcriptomi...
Article
Full-text available
Active co-delivery of tumor antigens (Ag) and α-galactosylceramide (α-GalCer), a potent agonist for invariant Natural Killer T (iNKT) cells, to cross-priming CD8α+ dendritic cells (DCs) was previously shown to promote strong anti-tumor responses in mice. Here, we designed a nanoparticle-based vaccine able to target human CD141+ (BDCA3+) DCs - the e...
Preprint
Full-text available
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. The major bacterial cause of COPD exacerbations is non-typeable Haemophilus influenzae (NTHi). This susceptibility to infection involves a defective production of interleukin (IL)-22 which plays an important role in mucosal defense. Prophylactic admi...
Article
Full-text available
Coronaviruses cause several human diseases, including severe acute respiratory syndrome. The global coronaviruses disease 2019 (COVID-19) pandemic has become a huge threat to humans. Intensive research on the pathogenic mechanisms used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed – notably in order to identify...
Preprint
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Most patients with COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), display neurological symptoms, and respiratory failure in certain cases could be of extra-pulmonary origin. With reports detecting SARS-CoV-2 in some post-mortem patient brains, the routes, targets and consequences of brain infection merit investiga...
Article
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Like all obligate intracellular pathogens, influenza A virus (IAV) reprograms host cell’s glucose and lipid metabolism to promote its own replication. However, the impact of influenza infection on white adipose tissue (WAT), a key tissue in the control of systemic energy homeostasis, has not been yet characterized. Here, we show that influenza infe...
Preprint
CD1d-restricted invariant Natural Killer T (iNKT) cells represent a unique class of T lymphocytes endowed with potent regulatory and effector immune functions. Although these functions are acquired during thymic ontogeny, the sequence of events that give rise to discrete effector subsets remains unclear. Using an unbiased single-cell transcriptomic...
Article
The progression of chronic obstructive pulmonary disease (COPD), a lung inflammatory disease being the 4th cause of death worldwide, is marked by acute exacerbations. These episodes are mostly caused by bacterial infections, frequently due to Streptococcus pneumoniae (Sp). This susceptibility to infection involved a defect in interleukin (IL)‐22 wh...
Article
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Secondary bacterial infections often complicate viral respiratory infections. We hypothesize that perturbation of the gut microbiota during influenza A virus (IAV) infection might favor respiratory bacterial superinfection. Sublethal infection with influenza transiently alters the composition and fermentative activity of the gut microbiota in mice....
Article
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Interleukin-7 (IL-7) is a critical cytokine in B- and T-lymphocyte development and maturation. Recent evidence suggests that IL-7 is a preferential homeostatic and survival factor for RORγt⁺ innate T cells such as natural killer T (NKT) cells, γδT cells, and mucosal-associated invariant T (MAIT) cells in the periphery. Given the important contribut...
Article
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The glycosphingolipid α-galactosylceramide (αGalCer), when presented by CD1d on antigen presenting cells, efficiently activates invariant natural killer T (iNKT) cells. Thereby, it modulates immune responses against tumors, microbial and viral infections and autoimmune diseases. Recently, the production of αGalCer by Bacteroidetes from the human gu...
Article
Influenza infections remain a burden on health care systems despite vaccination programs and marketed antiviral drugs. Immunomodulation through activation of innate sensors could represent innovative approaches to fight the flu. This study evaluated the ability of flagellin, agonist of Toll-like receptor 5 (TLR5), to control the replication of infl...
Article
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CD1d-restricted invariant natural killer T (iNKT) cells represent a heterogeneous population of lipid-reactive T cells that are involved in many immune responses, mediated through T-cell receptor (TCR)–dependent and/or independent activation. Although numerous microbial lipid antigens (Ags) have been identified, several lines of evidence have sugge...
Data
Expression and Ag presentation capacity of CD1d on DCs from Cers2 null mice. (A) Representative FACS plot of BMDCs from Cers2+/+ and Cers2−/− mice (gated on live CD45+ cells) is shown in the left panel. Histogram for CD1d surface expression on DCs of Cers2+/+ and Cers2−/− mice is shown in the right panel. Isotype controls for CerS2+/+ and CerS2−/−...
Data
C24:1 GM3 and C24:1 GD3 do not induce splenic conventional T cell proliferation. CTV-labeled spleen cells from C57BL/6 mice were cultured in absence or presence of α-GalCer (100 ng/ml), C24:1 GM3 (6.5μM), or GD3 (6.5μM) in complete RPMI plus IL-2. After 72 h, cells were harvested and analyzed by flow cytometry for CTV detection in live conventional...
Data
Reactivity of the 2C12 iNKT cell hybridoma towards synthetic gangliosides. DCs derived from WT mice were cultured with the mouse iNKT hybridoma 2C12 in presence of purified glycolipids at the indicated concentrations or vehicle in complete RPMI media supplemented with 5% FCS for 24 h. iNKT cell response was judged based on IL-2 production. Means ±...
Data
Stereo-controlled synthesis of GM3 (C24:1). (TIF)
Data
Bovine buttermilk-derived gangliosides do not activate iNKT cells. DCs derived from WT mice were cultured with the mouse iNKT hybridoma DN32.D3 in presence of α-GalCer (20 ng/ml), bovine buttermilk GM3 (10 μM) and bovine buttermilk GD3 (10μM), or vehicle in complete RPMI media supplemented with 5% FCS for 24 h. iNKT cell response was measured based...
Data
Comparison of 1H NMR spectra of GD3 (C24:1, stereo-controlled versus general). 1H NMR, proton nuclear magnetic resonance. (TIF)
Data
CD1d blockade abrogates lung iNKT cell activation upon C24:1 ganglioside instillation. Lung iNKT cells from vehicle-, α-GalCer- or C24:1 GM3-treated mice (12 h) were screened for intracellular IFNγ production. Mice were intraperitoneally pretreated (4 h prior glycolipid instillation) with either an isotype control mAb (LTF2, 500 μg/mouse) or an ant...
Article
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Despite the widespread application of vaccination programs and antiviral drug treatments, influenza viruses are still among the most harmful human pathogens. Indeed, influenza results in significant seasonal and pandemic morbidity and mortality. Furthermore, severe bacterial infections can occur in the aftermath of influenza virus infection, and co...
Data
Stereo-controlled synthesis of GD3 (C24:1). (TIF)
Data
Pulse timing on DCs influences ganglioside activity on iNKT cell hybridomas. DCs derived from WT mice were pulsed with C24:1 GM3, C24:1 GD3, or vehicle for the indicated amount of time. Then, cells were extensively washed and cultured with the iNKT cell hybridoma DN32.D3 for 24 h. iNKT cell response was judged based on IL-2 production. Means ± SEM...
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Numerical data used in this study. Numeric data shown in separate excel spreadsheets. (XLSX)
Data
Synthesis of β-GlcCer. β-GlcCer, β-glucosylceramide. (TIF)
Data
HILIC-MS2 analyses of stereo-controlled β-GlcCer. HILIC-MS2 of stereo-controlled β-GlcCer and an α/β-GlcCer mixture. α/β-GlcCer, α/β-glucosylceramide; HILIC-MS2, hydrophilic interaction liquid chromatography-tandem mass spectrometry. (TIF)
Data
HPLC of stereo-controlled GD3 (C24:1). HPLC, high-pressure liquid chromatography. (TIF)
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Thermophoretic analysis of NT647-labelled mCD1d-β-GlcCer interaction. Changes in thermophoresis of a titration of 125 nM NT647-labeled mCD1d with increasing concentrations of C24:1 β-GlcCer are expressed as change of the normalized fluorescence (ΔFnorm = FHot/Fcold) and plotted. Line is a fit with Michaelis–Menten kinetics of ΔFnorm mean ± SD for e...
Data
Instillation of C16:0 GD3 does not lead to lung iNKT cell activation. Lung iNKT cells from vehicle- or C16:0 GD3-treated mice (12 h) were screened for intracellular IFNγ and IL-17A production. Individual values and means ± SEM from two independent experiments are shown (5 mice/group) for panel. Underlying data used in the generation of this figure...
Data
Comparison of 1H NMR spectra of GM3 (C24:1, stereo-controlled versus general). 1H NMR, proton nuclear magnetic resonance. (TIF)
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LC-MS of stereo-controlled GD3 (C24:1). LC-MS, liquid chromatography-mass spectrometry. (TIF)
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LC-MS of stereo-controlled GM3 (C24:1). LC-MS, liquid chromatography-mass spectrometry. (TIF)
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HPLC of stereo-controlled GM3 (C24:1). HPLC, high-pressure liquid chromatography. (TIF)
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N-acyl chain analysis of DC-derived versus buttermilk-derived GM3. The acyl chain composition of GM3 from mouse unstimulated DCs or commercial bovine buttermilk was measured and compared by ES(-)-LC-MS/MS. Two sets of samples were measured and indicated as mean values. DC, dendritic cell; ES(-)-LC-MS/MS, electrospray(-)-liquid chromatography-mass s...
Article
Pneumococcal infections remain a major public health concern worldwide. The currently available vaccines in the market are based on pneumococcal capsular polysaccharides but they still need to be improved to secure an optimal coverage notably in population at risk. To circumvent this, association of virulence pneumococcal proteins to the polysaccha...
Data
(A) Mice were infected i.n. with H3N2 virus. Gating strategy to analyze total lung cDCs (Siglec-F-CD11c+MHCII+CD64-) and cDC subsets (CD172α+CD24+ and CD172α-CD24++) at day 0 (left panel) and 4dpi (right panel) is shown. (B) Gating strategy to analyze BM MDPs (Lin-CD117+CD135+CD115+), CDPs (Lin-CD117lowCD135+CD11c-CD115+) and pre-DCs (Lin-CD11c+MHC...
Data
Gating strategy to analyze spleen and lung pre-DCs. Lineage cocktail: Ter119, CD3, NK1.1, CD45RB220, Ly6G is shown. (TIF)
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(A) Gating strategy to analyze Flt3-L-generated BM DC subsets is shown. The remaining cells (CD11c-MHCII-) were CD11b-CD115-. (B) BM-derived cells in the presence of Flt3-L, were stimulated with LPS (100ng/ml) for 24h and IL-10 was quantified in the supernatant. Means ± SEM of 4 mice are represented. (TIF)
Data