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      Mechanisms of HIV-immunologic non-responses and research trends based on gut microbiota

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          Abstract

          With the increasing number of people with HIV (PWH) and the use of antiretroviral treatment (ART) for PWH, HIV has gradually become a chronic infectious disease. However, some infected individuals develop issues with immunologic non-responses (INRs) after receiving ART, which can lead to secondary infections and seriously affect the life expectancy and quality of life of PWH. Disruption of the gut microbiota is an important factor in immune activation and inflammation in HIV/AIDS, thus stabilizing the gut microbiota to reduce immune activation and inflammation and promoting immune reconstitution may become a direction for the treatment of HIV/AIDS. This paper, based on extensive literature review, summarizes the definition, mechanisms, and solutions for INRs, starting from the perspective of gut microbiota.

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          Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier.

          Emerging evidence supports a pathological link between vitamin D deficiency and the risk of inflammatory bowel disease (IBD). To explore the mechanism we used the dextran sulfate sodium (DSS)-induced colitis model to investigate the role of the vitamin D receptor (VDR) in mucosal barrier homeostasis. While VDR(+/+) mice were mostly resistant to 2.5% DSS, VDR(-/-) mice developed severe diarrhea, rectal bleeding, and marked body weight loss, leading to death in 2 wk. Histological examination revealed extensive ulceration and impaired wound healing in the colonic epithelium of DSS-treated VDR(-/-) mice. Severe ulceration in VDR(-/-) mice was preceded by a greater loss of intestinal transepithelial electric resistance (TER) compared with VDR(+/+) mice. Confocal and electron microscopy (EM) revealed severe disruption in epithelial junctions in VDR(-/-) mice after 3-day DSS treatment. Therefore, VDR(-/-) mice were much more susceptible to DSS-induced mucosal injury than VDR(+/+) mice. In cell cultures, 1,25-dihydroxy-vitamin D(3) [1,25(OH)(2)D(3)] markedly enhanced tight junctions formed by Caco-2 monolayers by increasing junction protein expression and TER and preserved the structural integrity of tight junctions in the presence of DSS. VDR knockdown with small interfering (si)RNA reduced the junction proteins and TER in Caco-2 monolayers. 1,25(OH)(2)D(3) can also stimulate epithelial cell migration in vitro. These observations suggest that VDR plays a critical role in mucosal barrier homeostasis by preserving the integrity of junction complexes and the healing capacity of the colonic epithelium. Therefore, vitamin D deficiency may compromise the mucosal barrier, leading to increased susceptibility to mucosal damage and increased risk of IBD.
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            Glycolysis – a key player in the inflammatory response

            The inflammatory response involves the activation of several cell types to fight insults caused by a plethora of agents, and to maintain the tissue homoeostasis. On the one hand, cells involved in the pro‐inflammatory response, such as inflammatory M1 macrophages, Th1 and Th17 lymphocytes or activated microglia, must rapidly provide energy to fuel inflammation, which is essentially accomplished by glycolysis and high lactate production. On the other hand, regulatory T cells or M2 macrophages, which are involved in immune regulation and resolution of inflammation, preferentially use fatty acid oxidation through the TCA cycle as a main source for energy production. Here, we discuss the impact of glycolytic metabolism at the different steps of the inflammatory response. Finally, we review a wide variety of molecular mechanisms which could explain the relationship between glycolytic metabolites and the pro‐inflammatory phenotype, including signalling events, epigenetic remodelling, post‐transcriptional regulation and post‐translational modifications. Inflammatory processes are a common feature of many age‐associated diseases, such as cardiovascular and neurodegenerative disorders. The finding that immunometabolism could be a master regulator of inflammation broadens the avenue for treating inflammation‐related pathologies through the manipulation of the vascular and immune cell metabolism.
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              Cutting Edge: 1,25-Dihydroxyvitamin D 3 Is a Direct Inducer of Antimicrobial Peptide Gene Expression

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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2699354Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2643440Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2599311Role: Role:
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                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                26 December 2024
                2024
                : 15
                : 1378431
                Affiliations
                [1] 1 Medical School of Shihezi University , Shihezi, China
                [2] 2 Department of Preventive Medicine, Medical School of Shihezi University , Shihezi, China
                Author notes

                Edited by: Elena Moreno, Ramón y Cajal University Hospital, Spain

                Reviewed by: Erick De La Torre Tarazona, Ramón y Cajal University Hospital, Spain

                Guo Mu, Zigong Fourth People’s Hospital, China

                Texca Tatevari Méndez López, Laboratorio Estatal de Salud Publica de Michoacan Vigilancia Epidemiologica, Mexico

                *Correspondence: Ke Li, 464342187@ 123456qq.com

                †These authors share first authorship

                ‡ORCID: Zhanpeng Xie, orcid.org/0009-0000-5719-6823

                Article
                10.3389/fimmu.2024.1378431
                11718445
                39802299
                3df0252b-1b4b-4e63-8300-36cdd09efd3a
                Copyright © 2024 Sun, Xie, Wu, Song, Zhang, Zhang, Cui, Liu and Li

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 January 2024
                : 12 December 2024
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 125, Pages: 11, Words: 5504
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by Xinjiang Production and Construction Corps Social Science Project (21YB08) and Shihezi University (Philosophy and Social Science) Fund (ZZZC202147).
                Categories
                Immunology
                Mini Review
                Custom metadata
                Viral Immunology

                Immunology
                hiv/aids,inrs,art,gut microbiota,traditional chinese medicine (tcm)
                Immunology
                hiv/aids, inrs, art, gut microbiota, traditional chinese medicine (tcm)

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