Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 219 - 219

Published: Jan. 31, 2024

Chronic Human Immunodeficiency Virus (HIV) infection remains a significant challenge to global public health. Despite advances in antiretroviral therapy (ART), which has transformed HIV from fatal disease into manageable chronic condition, definitive cure elusive. One of the key features is immune activation and inflammation, are strongly associated with, predictive of, progression, even patients successfully treated with suppressive ART. inflammation characterized by persistent cell metabolic dysregulation, cellular exhaustion dysfunction. This review aims summarize current knowledge interplay between metabolism, T dysfunction infection, also discusses use humanized mice models study pathogenesis develop novel therapeutic strategies.

Language: Английский

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Vaccine- and natural infection-induced mechanisms that could modulate vaccine safety

Toxicology Reports, Journal Year: 2020, Volume and Issue: 7, P. 1448 - 1458

Published: Jan. 1, 2020

A degraded/dysfunctional immune system appears to be the main determinant of serious/fatal reaction viral infection (for COVID-19, SARS, and influenza alike). There are four major approaches being employed or considered presently augment strengthen system, in order reduce adverse effects exposure. The three that focused mainly on augmenting based concept pandemics/outbreaks can controlled/prevented while maintaining immune-degrading lifestyles followed by much global population. fourth approach is identifying introducing measures aimed at strengthening intrinsically minimize future pandemics/outbreaks. Specifically, are: 1) restricting exposure virus; 2) providing reactive/tactical treatments load; 3) developing vaccines prevent, least attenuate, infection; 4) intrinsically, a) those factors contribute degrading then eliminating/reducing them as comprehensively, thoroughly, rapidly possible, b) replacing eliminated with immune-strengthening factors. This paper focuses vaccine safety. COVID-19 treatment choice national/international level. Vaccine development has been accelerated achieve this goal relatively near-term, questions have arisen whether safety been/is being/will compromised pursuit a shortened time. myriad mechanisms related vaccine-induced, natural infection-induced, infections could adversely impact effectiveness summarizes many mechanisms.

Language: Английский

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The metabolic consequences of HIV/TB co-infection

BMC Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(1)

Published: Aug. 18, 2023

The synergy between the human immunodeficiency virus (HIV) and Mycobacterium tuberculosis during co-infection of a host is well known. While this known to be driven by immunological deterioration, metabolic mechanisms that contribute associated disease burden experienced HIV/tuberculosis (TB) remain poorly understood. Furthermore, while anti-HIV treatments suppress viral replication, these therapeutics give rise disruption adaptations beyond induced only infection or disease.In study, serum profiles healthy controls, untreated HIV-negative TB-positive patients, HIV/TB co-infected patients on antiretroviral therapy (ART), were measured using two-dimensional gas chromatography time-of-flight mass spectrometry. Since no global profile for effect ART has been published date, pilot study aimed elucidate general areas metabolism affected such conditions.HIV/TB significant changes host's lipid protein metabolism, with additional microbial product translocation from gut blood. results suggest HIV augments TB synergistically, at least in part, contributing increased inflammation, oxidative stress, ART-induced mitochondrial damage, its detrimental effects health, which turn, affects energy availability. reverses trends some extent but not controls.This generated several new hypotheses could direct future studies, combined other research techniques methodologies further underlying changes.

Language: Английский

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Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflect the Severity for the Acute and Chronic Infectious Diseases

Biomolecules, Journal Year: 2021, Volume and Issue: 11(3), P. 430 - 430

Published: March 15, 2021

Galectin-9 (Gal-9) is a β-galactoside-binding lectin capable of promoting or suppressing the progression infectious diseases. This protein susceptible to cleavage its linker-peptides by several proteases, and resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) C-terminal CRD, bind various glycans. It has been suggested that full-length (FL)-Gal-9 truncated (Tr)-Gal-9s could exert different functions from one another via their glycan-binding activities. We propose FL-Gal-9 regulates pathogenesis diseases, including human immunodeficiency virus (HIV) infection, HIV co-infected with opportunistic infection (HIV/OI), dengue, malaria, leptospirosis, tuberculosis (TB). also suggest blood levels reflect severity HIV/OI, those Tr-Gal-9 markedly HIV/OI. Recently, matrix metallopeptidase-9 (MMP-9) was be an indicator respiratory failure coronavirus disease 2019 (COVID-19) as well useful for differentiating pulmonary extrapulmonary TB. The protease may lead uncontrolled hyper-immune activation, cytokine storm. In summary, Gal-9 potential acute chronic

Language: Английский

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Tuberculosis diagnostics: overcoming ancient challenges with modern solutions

Emerging Topics in Life Sciences, Journal Year: 2020, Volume and Issue: 4(4), P. 435 - 448

Published: Dec. 1, 2020

Rapid, sensitive, accurate and portable diagnostics are a mainstay of modern medicine. Tuberculosis is disease that has been with us since time immemorial and, despite the fact it can be treated cured, still remains world's biggest infectious killer, taking lives millions annually. There have important developments in diagnostic devices for tuberculosis however, these often prone to error, expensive, lack necessary sensitivity or accuracy crucially, not sufficiently thus applicable remote, rural areas, where they most needed. Modern solutions emerging past decade, seeking overcome many inhibiting issues this field by utilising recent advances molecular biology, genetics sequencing even completely ‘reinventing wheel’, developing novel unprecedented techniques. In mini review, challenges arising from historical methods diagnosing discussed, followed outlaying their particular appropriateness regions world endemic. Subsequently, more new technological advancements as ‘modern weapons’ battle defeat associated reviewed, finally an outlook presented, highlighting future under development, which envisioned lay platform improvements delivering timely intervention, reduce immense expense burden on healthcare systems worldwide, while saving eventually, may enable eradication ancient disease.

Language: Английский

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A novel humanized mouse model for HIV and tuberculosis co-infection studies

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 10, 2024

Background Tuberculosis (TB), caused by Mycobacterium tuberculosis ( Mtb ), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. HIV infection decreases CD4+ T cell levels markedly increasing co-infections. An appropriate animal model for HIV/ co-infection that can recapitulate the diversity of immune response in humans during would facilitate basic and translational research infections. Herein, we describe novel humanized mouse model. Methods irradiated NSG-SGM3 mice were transplanted with CD34+ hematopoietic stem cells, humanization was monitored staining various markers flow cytometry. They challenged and/or , depletion viral load over time. Before necropsy, live subjected pulmonary function test CT scan, after sacrifice, lung spleen homogenates used determine (CFU) cytokine/chemokine multiplex assay, sections analyzed histopathology. sera metabolomics analysis. Results Our able engraft which then differentiated into full-lineage subsets. After these showed decrease counts overtime elevated sera, similar pattern humans. Additionally, infections both lungs spleen, induced granulomatous lesions lungs. Distinct metabolomic profiles also observed tissues from different groups Conclusion are pathogenic effects at pathological, immunological metabolism therefore reproducible small studying co-infection.

Language: Английский

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Metabolomics as a Tool to Investigate HIV/TB Co-Infection

Frontiers in Molecular Biosciences, Journal Year: 2021, Volume and Issue: 8

Published: Oct. 20, 2021

The HIV/AIDS (human immunodeficiency virus/acquired syndrome) and tuberculosis (TB) pandemics are perpetuated by a significant global burden of HIV/TB co-infection. synergy between HIV Mycobacterium ( Mtb ) during co-infection host is well established. While this known to be driven immunological deterioration, the metabolic mechanisms thereof remain poorly understood. Metabolomics has been applied study various aspects infection separately, yielding insights into infection- treatment-induced adaptations experienced host. Despite contributions that metabolomics made field, approach not yet systematically characterize co-infected state. Considering limited studies have published date, review briefly summarizes what regarding synergism from conventional perspective. It then explores as tool for improved characterization in context previously human-related TB investigations, respectively addressing gaps existing knowledge based on similarities deviating trends reported these studies.

Language: Английский

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The correlation between immune profiles and pathological changes in pulmonary tuberculosis granulomas revealed by bioinformatic analysis and experimental validation

Tuberculosis, Journal Year: 2025, Volume and Issue: 152, P. 102614 - 102614

Published: Feb. 11, 2025

Language: Английский

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Acute-phase proteins as biomarkers of inflammation in HIV patients with latent tuberculosis: a prospective study

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 30, 2025

Tuberculosis (TB) remains the primary cause of death among individuals infected with HIV, increasing risk contracting TB by up to 26 times. This co-infection complicates diagnosis and treatment TB, ultimately affecting outcomes adversely. Acute-phase proteins (APPs), markers inflammation, are significantly elevated during infections serve as critical indicators inflammation resulting from infectious diseases. In this prospective study, HIV-positive at antiretroviral therapy (ART) clinics were screened for latent tuberculosis infection (LTBI) before starting isoniazid (INH) prophylaxis. Initially, 101 patients enrolled, 71 completing a six-month follow-up on INH LTBI was diagnosed using QuantiFERON-TB Gold plus, categorizing participants (n=30) without (n=71). Plasma levels alpha-2-macroglobulin (A2M), C-reactive protein (CRP), serum amyloid P (SAP), haptoglobin, ferritin, soluble transferrin receptor (sTFR), apotransferrin, hepcidin, S100A8/A9 assessed multiplex quantikine assays.At baseline, A2M, CRP, SAP, S100A9 in compared those (A2M, p=0.005; p<0.001; p=0.0006; p=0.001; S100A9, p=0.001). Following six months prophylaxis, significant reductions these observed both groups, suggesting reduction inflammation. Our findings indicate that baseline profile APPs can effectively reflect inflammatory status HIV LTBI. These tend decrease following effective treatment, underscoring their potential utility monitoring disease progression response vulnerable population.

Language: Английский

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Advances in host-directed therapy for tuberculosis and HIV coinfection: enhancing immune responses

Trends in Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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