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      Pre-Digested Protein Enteral Nutritional Supplementation Enhances Recovery of CD4 + T Cells and Repair of Intestinal Barrier in HIV-Infected Immunological Non-Responders

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          Abstract

          AIDS patients with immune non-response are prone to malnutrition, intestinal barrier damage, thus aggravating chronic immune activation and inflammation. However, nutritional interventions targeting malnutrition may be beneficial to restore immune function, improve clinical outcomes, and reduce mortality remains largely unclear. This work aimed to evaluate the efficacy of a nutritional supplement in HIV-infected immune non-responders (INRs). The subjects received oral supplementation of a pre-digested protein nutrition formula for three months. We show that the CD4 + T and CD8 + T cell counts were significantly increased after supplementation of the pre-digested enteral nutritional supplement. Among all pro-inflammatory cytokines in the serum, only IL-1β level was significantly decreased, while TNF-β was significantly increased ( P < 0.05). The levels of intestinal mucosal damage markers, diamine oxidase (DAO), D-lactic acid (D-lactate), and lipopolysaccharide (LPS), decreased significantly ( P < 0.05) after the nutritional intervention. Moreover, at month 3 after the intervention, the body weight, body mass index, albumin, and hemoglobin of all subjects were significantly increased ( P < 0.05). The correlation analysis demonstrated a significantly negative correlation of CD4 + T cell count with levels of DAO (r = -0.343, P = 0.004), D-lactate (r = -0.250, P = 0.037), respectively, and a significantly positive correlation of IL-1β level with levels of DAO (r = 0.445, P < 0.001), D-lactate (r = 0.523, P < 0.001), and LPS (r = 0.622, P < 0.001). We conclude that the pre-digested enteral nutrition supplement is effective for HIV-infected INRs.

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          Most cited references59

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          Toll-like receptor signalling.

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            Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins.

            A panel of antigen-specific mouse helper T cell clones was characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished. Type 1 T helper cells (TH1) produced IL 2, interferon-gamma, GM-CSF, and IL 3 in response to antigen + presenting cells or to Con A, whereas type 2 helper T cells (TH2) produced IL 3, BSF1, and two other activities unique to the TH2 subset, a mast cell growth factor distinct from IL 3 and a T cell growth factor distinct from IL 2. Clones representing each type of T cell were characterized, and the pattern of lymphokine activities was consistent within each set. The secreted proteins induced by Con A were analyzed by biosynthetic labeling and SDS gel electrophoresis, and significant differences were seen between the two groups of T cell line. Both types of T cell grew in response to alternating cycles of antigen stimulation, followed by growth in IL 2-containing medium. Examples of both types of T cell were also specific for or restricted by the I region of the MHC, and the surface marker phenotype of the majority of both types was Ly-1+, Lyt-2-, L3T4+, Both types of helper T cell could provide help for B cells, but the nature of the help differed. TH1 cells were found among examples of T cell clones specific for chicken RBC and mouse alloantigens. TH2 cells were found among clones specific for mouse alloantigens, fowl gamma-globulin, and KLH. The relationship between these two types of T cells and previously described subsets of T helper cells is discussed.
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              Obesity induces a phenotypic switch in adipose tissue macrophage polarization.

              Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or "alternatively activated" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or "classically activated" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                24 December 2021
                2021
                : 12
                : 757935
                Affiliations
                [1] 1 National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University , Kunming, China
                [2] 2 Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University , Kunming, China
                [3] 3 Department of Gastrointestinal and Hernia Surgery, First Affiliated Hospital of Kunming Medical University , Kunming, China
                [4] 4 Department of Dermatology, Second People’s Hospital of Dali City , Dali, China
                [5] 5 School of Medicine, Yunnan University , Kunming, China
                Author notes

                Edited by: Weiming Tang, University of North Carolina at Chapel Hill, United States

                Reviewed by: Kongyang Ma, Sun Yat-sen University, China; Aijuan Zheng, Chinese Academy of Agricultural Sciences (CAAS), China

                *Correspondence: Kun-Hua Wang, kunhuawang1@ 123456163.com ; Yi-Qun Kuang, yq610433@ 123456hotmail.com

                †These authors have contributed equally to this work

                This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2021.757935
                8741150
                35003070
                fe7ed363-8ed9-42e2-b2cd-e640c447dd96
                Copyright © 2021 Geng, Zhang, Wang, Xu, Lu, Zhang, Gao, Wang and Kuang

                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
                : 13 August 2021
                : 13 December 2021
                Page count
                Figures: 6, Tables: 2, Equations: 0, References: 59, Pages: 11, Words: 5368
                Funding
                Funded by: National Natural Science Foundation of China-China Academy of General Technology Joint Fund for Basic Research , doi 10.13039/501100019492;
                Categories
                Immunology
                Original Research

                Immunology
                hiv/aids,immunological non-response,enteral nutrition,intestinal barrier function,inflammation

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