Biology subjects

Riou, C.

Publications and source records attributed to Riou, C..

7 recordsLinked to original sources

bioRxiv2022

Blood and site of disease inflammatory profiles differ in HIV-1-infected pericardial tuberculosis patients

ObjectivesTo better understand the pathogenesis of pericardial tuberculosis (PCTB), we sought to characterize the systemic inflammatory profile in HIV-1-infected participants with latent TB infection (LTBI), pulmonary TB (PTB) and PCTB. MethodsUsing Luminex, we measured 39 analytes in pericardial fluid (PCF) and paired plasma from 18 PCTB participants, and plasma from 16 LTBI and 20 PTB. Follow-up plasma samples were also obtained from PTB and PCTB participants. HLA-DR expression on Mtb-specific CD4 T cells was measured in baseline samples using flow cytometry. ResultsAssessment of the overall systemic inflammatory profile by principal component analysis showed that the inflammatory profile of active TB participants was distinct from the LTBI group, while PTB patients could not be distinguished from those with PCTB. In the LTBI group, 12 analytes showed a positive association with plasma HIV-1 viral load, and most of these associations were lost in the diseased groups. When comparing the inflammatory profile between PCF and paired blood, we found that the concentrations of most analytes (24/39) were elevated at site of disease. However, the inflammatory profile in PCF partially mirrored inflammatory events in the blood. After TB treatment completion, the overall plasma inflammatory profile reverted to those observed in the LTBI group. Lastly, HLA-DR expression showed the best performance for TB diagnosis compared to previously described biosignatures built from soluble markers. ConclusionOur results describe the inflammatory profile associated with PTB and PCTB and emphasize the potential role of HLA-DR as a promising biomarker for TB diagnosis.

immunology↗

bioRxiv2022

Phenotypic profile of Mycobacterium tuberculosis-specific CD4 T cell responses in HIV-positive patients who develop Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome

BackgroundTuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of co-treatment for TB and HIV-1. We characterized Mtb-specific CD4 T cell phenotype and transcription factor profile associated with the development of TB-IRIS. MethodsWe examined the role of CD4 T-cell transcription factors in a murine model of mycobacterial IRIS. In humans, we compared longitudinally on antiretroviral therapy (ART) the magnitude, activation, transcription factor profile and cytotoxic potential of Mtb-specific CD4 T cells between TB-IRIS (n=25) and appropriate non-IRIS control patients (n=18) using flow cytometry. ResultsIn the murine model, CD4 T cell expression of Eomes, but not Tbet, was associated with experimentally induced IRIS. In patients, TB-IRIS onset was associated with the expansion of Mtb-specific IFN{gamma}+CD4 T cells (p=0.039). TB-IRIS patients had higher HLA-DR expression (p=0.016), but no differences in the expression of T-bet or Eomes were observed. At TB-IRIS onset, Eomes+Tbet+Mtb-specific IFN{gamma}+CD4+ T cells showed higher expression of Granzyme B in TB-IRIS patients (p=0.026). ConclusionWhile the murine model of MAC-IRIS suggests that Eomes+CD4 T cells underly IRIS, TB-IRIS was not associated with Eomes expression in patients. Mtb-specific IFN{gamma}+CD4 T cell responses in TB-IRIS patients are differentiated, highly activated and potentially cytotoxic.

immunology↗

bioRxiv2022

Profile of Mycobacterium tuberculosis-specific CD4 T cells at the site of disease and blood in pericardial tuberculosis

Our understanding of the immune response at the site of disease in extra-pulmonary tuberculosis (EPTB) is still limited. In this study, using flow cytometry, we defined the pericardial fluid (PCF) cellular composition and compared the phenotypic and functional profile of Mycobacterium tuberculosis (Mtb)-specific T cells between PCF and whole blood in 16 patients with pericardial TB (PCTB). We found that lymphocytes were the predominant cell type in PCF in PCTB, with a preferential influx of CD4 T cells. The frequencies of TNF- producing myeloid cells and Mtb-specific T cells were significantly higher in PCF compared to blood. Mtb-specific CD4 T cells in PCF exhibited a distinct phenotype compared to those in blood, with greater GrB expression and lower CD27 and KLRG1 expression. We observed no difference in the production IFN{gamma}, TNF or IL-2 by Mtb-specific CD4 T cells between the two compartments, but MIP-1{beta} production was lower in the PCF T cells. Bacterial loads in the PCF did not relate to the phenotype or function of Mtb-specific CD4 T cells. Upon anti-tubercular treatment completion, HLA-DR, Ki-67 and GrB expression was significantly decreased, and relative IL-2 production was increased in peripheral Mtb-specific CD4 T cells. Overall, using a novel and rapid experimental approach to measure T cell response ex vivo at site of disease, these results provide novel insight into molecular mechanisms and immunopathology at site of TB infection of the pericardium.

immunology↗

bioRxiv2021

Eosinophils are an integral component of the pulmonary granulocyte response in Tuberculosis and promote host resistance in mice

Host resistance to Mycobacterium tuberculosis infection requires the activities of multiple leukocyte subsets, yet the roles of the different innate effector cells during tuberculosis are incompletely understood. Here we uncover an unexpected association between eosinophils and Mtb infection. In humans, eosinophils are decreased in the blood but enriched in resected human tuberculosis lung lesions and autopsy granulomas. Influx of eosinophils is also evident in infected zebrafish, mice, and nonhuman primate granulomas, where they are functionally activated and degranulate. Importantly, employing complementary genetic models of eosinophil deficiency, we demonstrate that, in mice, eosinophils are required for optimal pulmonary bacterial control and host survival after Mtb infection. Collectively, our findings uncover an unexpected recruitment of eosinophils to the infected lung tissue and a protective role for these cells in the control of Mtb infection in mice.

immunology↗

bioRxiv2019

Th22 cells are a major contributor to the mycobacterial CD4+ T cell response and are depleted during HIV infection

HIV-1 infection substantially increases the risk of developing tuberculosis (TB). Some mechanisms, such as defects in the Th1 response to Mycobacterium tuberculosis (M.tb) in HIV-infected individuals have been widely reported. However, Th1-independent mechanisms also contribute to protection against TB. To identify a broader spectrum of defects in TB immunity during HIV infection, we examined IL-17 and IL-22 production in response to mycobacterial antigens in individuals with latent TB infection (LTBI) and HIV co-infection. Upon stimulating with mycobacterial antigens, we observed a distinct CD4+ T helper lineage producing IL-22 in the absence of IL-17 and IFN-{gamma}. Th22 cells were present at high frequencies in response to mycobacterial antigens in blood and contributed up to 50% to the CD4+ T cell response to mycobacteria, comparable in magnitude to the IFN-{gamma} Th1 response (median 0.91% and 0.55%, respectively). Phenotypic characterization of Th22 cells revealed that their memory differentiation was similar to M.tb-specific Th1 cells (i.e. predominantly early-differentiated CD45RO+CD27+ phenotype). Moreover, CCR6 and CXCR3 expression profiles of Th22 cells were similar to Th17 cells, while their CCR4 and CCR10 expression patterns displayed an intermediate phenotype between Th1 and Th17 cells. Strikingly, mycobacterial IL-22 responses were three-fold lower in HIV-infected individuals compared to uninfected individuals, and the magnitude of responses correlated inversely with HIV viral load. These data provide important insights into mycobacteria-specific T helper subsets and suggest a potential role for IL-22 in protection against TB during HIV infection. Further studies are needed to fully elucidate the role of IL-22 in protective TB immunity.

immunology↗

bioRxiv2017

DiscoSnp-RAD: de novo detection of small variants for population genomics

We present an original method to de novo call variants for Restriction site associated DNA Sequencing (RAD-Seq). RAD-Seq is a technique characterized by the sequencing of specific loci along the genome, that is widely employed in the field of evolutionary biology since it allows to exploit variants (mainly SNPs) information from entire populations at a reduced cost. Common RAD dedicated tools, as STACKS or IPyRAD, are based on all-versus-all read comparisons, which require consequent time and computing resources. Based on the variant caller DiscoSnp, initially designed for shotgun sequencing, DiscoSnp-RAD avoids this pitfall as variants are detected by exploring the De Bruijn Graph built from all the read datasets. We tested the implementation on RAD data from 259 specimens of Chiastocheta flies, morphologically assigned to 7 species. All individuals were successfully assigned to their species using both STRUCTURE and Maximum Likelihood phylogenetic reconstruction. Moreover, identified variants succeeded to reveal a within species structuration and the existence of two populations linked to their geographic distributions. Furthermore, our results show that DiscoSnp-RAD is at least one order of magnitude faster than state-of-the-art tools. The overall results show that DiscoSnp-RAD is suitable to identify variants from RAD data, and stands out from other tools due to his completely different principle, making it significantly faster, in particular on large datasets.\n\nLicenseGNU Affero general public license\n\nAvailabilityhttps://github.com/GATB/DiscoSnp\n\nContactjeremy.gauthier@inria.fr

bioinformatics↗

bioRxiv2017

DiscoSnp++: de novo detection of small variants from raw unassembled read set(s)

MotivationNext Generation Sequencing (NGS) data provide an unprecedented access to life mechanisms. In particular, these data enable to detect polymorphisms such as SNPs and indels. As these polymorphisms represent a fundamental source of information in agronomy, environment or medicine, their detection in NGS data is now a routine task. The main methods for their prediction usually need a reference genome. However, non-model organisms and highly divergent genomes such as in cancer studies are extensively investigated.\n\nResultsWe propose DiscoSnp++, in which we revisit the DiscoSnp algorithm. DiscoSnp++ is designed for detecting and ranking all kinds of SNPs and small indels from raw read set(s). It outputs files in fasta and VCF formats. In particular, predicted variants can be automatically localized afterwards on a reference genome if available. Its usage is extremely simple and its low resource requirements make it usable on common desktop computers. Results show that DiscoSnp++ performs better than state-of-the-art methods in terms of computational resources and in terms of results quality. An important novelty is the de novo detection of indels, for which we obtained 99% precision when calling indels on simulated human datasets and 90% recall on high confident indels from the Platinum dataset.\n\nLicenseGNU Affero general public license\n\nAvailabilityhttps://github.com/GATB/DiscoSnp\n\nContactpierre.peterlongo@inria.fr

bioinformatics↗