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      NK cell spatial dynamics and IgA responses in gut-associated lymphoid tissues during SIV infections

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          Abstract

          HIV infection induces tissue damage including lymph node (LN) fibrosis and intestinal epithelial barrier disruption leading to bacterial translocation and systemic inflammation. Natural hosts of SIV, such as African Green Monkeys (AGM), do not display tissue damage despite high viral load in blood and intestinal mucosa. AGM mount a NK cell-mediated control of SIVagm replication in peripheral LN. We analyzed if NK cells also control SIVagm in mesenteric (mes) LN and if this has an impact on gut humoral responses and the production of IgA known for their anti-inflammatory role in the gut. We show that CXCR5 + NK cell frequencies increase in mesLN upon SIVagm infection and that NK cells migrate into and control viral replication in B cell follicles (BCF) of mesLN. The proportion of IgA+ memory B cells were increased in mesLN during SIVagm infection in contrast to SIVmac infection. Total IgA levels in gut remained normal during SIVagm infection, while strongly decreased in intestine of chronically SIVmac-infected macaques. Our data suggest an indirect impact of NK cell-mediated viral control in mesLN during SIVagm infection on preserved BCF function and IgA production in intestinal tissues.

          Abstract

          Differences between pathogenic and non-pathogenic SIV infections are investigated, in terms of NK cell location, function and IgA responses in gut associated lymphoid tissues (mesenteric lymph nodes, jejunum, ileon, colon).

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          Most cited references61

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

            In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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              Defining total-body AIDS-virus burden with implications for curative strategies.

              In the quest for a functional cure or the eradication of HIV infection, it is necessary to know the sizes of the reservoirs from which infection rebounds after treatment interruption. Thus, we quantified SIV and HIV tissue burdens in tissues of infected nonhuman primates and lymphoid tissue (LT) biopsies from infected humans. Before antiretroviral therapy (ART), LTs contained >98% of the SIV RNA+and DNA+cells. With ART, the numbers of virus (v) RNA+ cells substantially decreased but remained detectable, and their persistence was associated with relatively lower drug concentrations in LT than in peripheral blood. Prolonged ART also decreased the levels of SIV- and HIV-DNA+cells, but the estimated size of the residual tissue burden of 108vDNA+cells potentially containing replication-competent proviruses, along with evidence of continuing virus production in LT despite ART, indicated two important sources for rebound following treatment interruption. The large sizes of these tissue reservoirs underscore challenges in developing 'HIV cure' strategies targeting multiple sources of virus production.
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                Author and article information

                Contributors
                mmuller@pasteur.fr
                Journal
                Commun Biol
                Commun Biol
                Communications Biology
                Nature Publishing Group UK (London )
                2399-3642
                7 July 2022
                7 July 2022
                2022
                : 5
                : 674
                Affiliations
                [1 ]GRID grid.508487.6, ISNI 0000 0004 7885 7602, Institut Pasteur, Unité HIV Inflammation and Persistance, , Université de Paris, ; Paris, France
                [2 ]GRID grid.508487.6, ISNI 0000 0004 7885 7602, Université Paris Diderot, Sorbonne Paris Cité, ; Paris, France
                [3 ]GRID grid.508487.6, ISNI 0000 0004 7885 7602, Institut Pasteur, Laboratory of Humoral Immunology, , Université de Paris, ; Paris, France
                [4 ]GRID grid.7429.8, ISNI 0000000121866389, INSERM U1222, ; Paris, France
                [5 ]GRID grid.457349.8, ISNI 0000 0004 0623 0579, CEA, Université Paris Sud 11, INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases, IDMIT, IBFJ, ; Fontenay-aux-Roses, France
                Author information
                http://orcid.org/0000-0001-8860-3938
                http://orcid.org/0000-0002-1896-5092
                http://orcid.org/0000-0003-2406-7536
                http://orcid.org/0000-0002-3854-2396
                Article
                3619
                10.1038/s42003-022-03619-y
                9262959
                35798936
                b81cc2fb-161a-4e0c-b96a-90064ac6965c
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 June 2021
                : 22 June 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000009, Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.);
                Award ID: R01AI143457
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100009060, Sidaction;
                Funded by: FundRef https://doi.org/10.13039/501100003762, Institut Pasteur;
                Funded by: We are grateful for the excellent contributions from the veterinarians and staff at the IDMIT Center (Benoit Delache, Jean-Marie Helies, and Raphaël Ho Tsong Fang). NH was supported by the Fondation J. Beytout and Institut Pasteur. PR was recipient of a PhD fellowship from the University Paris Diderot, Sorbonne Paris Cité and supported by the NIH (R01AI143457) and Institut Pasteur. CaP was recipient of a Roux-Cantarini Postdoctoral Fellowship. Cy.P. was the recipient of an ANRS post-doctoral fellowship. We would like to acknowledge grant support from Sidaction and ANRS to MMT. H.M. received core grants from the Institut Pasteur, the INSERM and the Milieu Intérieur Program (ANR-10-LABX-69-01) and was supported by an ANRS grant. We gratefully acknowledge the support to IDMIT from the French government: Investments for the Future program for infrastructures (PIA) through the ANR-11-INBS-0008 grant as well as from the PIA grant ANR-10-EQPX-02-01 to the FlowCyTech facility at IDMIT. We equally acknowledge the Investments for Future grant ANR-10–INSB–04 to support the UtechS Photonic BioImaging (Imagopole) and C2RT facilities at Institut Pasteur.
                Categories
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                © The Author(s) 2022

                hiv infections,infection,mucosal immunology,nk cells
                hiv infections, infection, mucosal immunology, nk cells

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