Cell Reports, Journal Year: 2024, Volume and Issue: 44(1), P. 115072 - 115072
Published: Dec. 17, 2024
Language: Английский
International Reviews of Immunology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 28
Published: April 17, 2025
Innate lymphoid cells (ILCs) have emerged as pivotal players in the field of immunology, expanding our understanding innate immunity beyond conventional paradigms. This comprehensive review delves into multifaceted world ILCs, beginning with their serendipitous discovery and traversing ontogeny heterogeneity. We explore distinct subsets ILCs unraveling intriguing plasticity, which adds a layer complexity to functional repertoire. As we journey through activities address role immune responses against various infections, categorizing interactions helminthic parasites, bacterial pathogens, fungal viral invaders. Notably, this offers detailed examination context specific such Mycobacterium tuberculosis, Citrobacter rodentium, Clostridium difficile, Salmonella typhimurium, Helicobacter pylori, Listeria monocytogenes, Staphylococcus aureus, Pseudomonas aeruginosa, Influenza virus, Cytomegalovirus, Herpes simplex severe acute respiratory syndrome coronavirus 2. selection aimed for exploration infectious contexts, opting microorganisms based on extensive research findings rather than considerations virulence or emergence. Furthermore, raise questions about potential resemblances between epithelial cells, shedding light interconnectedness within mucosal microenvironment. The culminates critical assessment therapeutic prospects targeting during infection, emphasizing promise novel immunotherapeutic targets. Nevertheless, due recent evolving understanding, effectively manipulating is challenging. Ensuring specificity safety while evaluating long-term effects clinical settings will be crucial.
Language: Английский
Citations
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Clinica Chimica Acta, Journal Year: 2025, Volume and Issue: 574, P. 120327 - 120327
Published: April 24, 2025
Language: Английский
Citations
0
Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 15
Published: May 8, 2025
Despite years of global efforts to combat tuberculosis (TB), Mycobacterium ( Mtb ), the causative agent this disease, continues haunt humankind making TB elimination a distant task. To comprehend pathogenic nuances organism, various in vitro, ex vivo and experimental models have been employed by researchers. This review focuses on salient features as well pros cons model systems for research. In vitro macrophage infection extensively used studying physiology. Animal provided us with great wealth information immensely contributed understanding pathogenesis host responses during infection. Additionally, they evaluation anti-mycobacterial drug therapy determining efficacy potential vaccine candidates. Advancements ‘omics’ based approaches enhanced our about host-pathogen interface. Although animal cornerstone research, none them is ideal that gives complete picture human infection, disease progression. Further, also discusses newer including three dimensional (3D)-tissue models, lung-on-chip model, granuloma their limitations TB. Thus, converging gained from tandem experiments will ultimately bridge gap exists
Language: Английский
Citations
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Frontiers in Applied Mathematics and Statistics, Journal Year: 2024, Volume and Issue: 10
Published: Jan. 31, 2024
Tuberculosis (TB), a disease caused by bacteria Mycobacterium tuberculosis (Mtb), remains one of the major infectious diseases humans with 10 million TB cases and 1.5 deaths due to worldwide yearly. Upon exposure new host Mtb, typically infect local site in lung, but over time, Mtb disseminates lung some extrapulmonary sites. The contribution various components such as immune cells dynamics its dissemination outside incompletely understood. Here we overview different types mathematical models used gain insights within-host Mtb; these include based on ordinary or partial differential equations (ODEs PDEs), stochastic simulation ODEs, agent-based (ABMs), hybrid (ODE-based linked ABMs). We illustrate results from several identify areas for future resesarch.
Language: Английский
Citations
2
Advanced Therapeutics, Journal Year: 2024, Volume and Issue: unknown
Published: July 5, 2024
Abstract Despite multiple treatments for tuberculosis (TB), there are ≈10 million new cases and 1.5 deaths annually, warranting the need therapeutics. Major clinical treatment issues include length of which is associated with patient non‐compliance; poor cellular drug penetration leading to generation drug‐resistant strains. This study underscores potential β‐glucan‐chitosan (CS) poly(lactic co‐glycolic) acid (PLGA) nanoparticles as a promising immunostimulatory adjunct TB treatment. To facilitate delivery alveolar macrophage, CS‐PLGA nanoparticle developed containing rifampin in core β‐glucan surface ligand, stimulate immune system. Mice administered single dose or free by oropharyngeal aspiration. Pharmacokinetic investigations reveal sustained release properties vivo, extending over week. Furthermore, comprehensive analysis indicates stimulation innate system, evidenced cytokine profiling, while concurrently revealing no detrimental effects on epithelium, indicated histological examination albumin lung leak assessment. These findings collectively establish strong foundation development novel adjuvant immunotherapy approach TB.
Language: Английский
Citations
2
Veterinary Research, Journal Year: 2024, Volume and Issue: 55(1)
Published: July 29, 2024
Abstract Infection of piglets with Glaesserella parasuis ( G. ) induces host immunosuppression. However, the mechanism underlying immunosuppression remains unclear. Activation PD-1/PD-L1 axis has been shown to trigger Baicalin possesses anti-inflammatory and immunomodulatory functions. whether baicalin inhibits activation thus alleviates not investigated. In this study, effect on attenuation piglet induced by was evaluated. Seventy were randomly divided into control group, infection levamisole BMS-1 25 mg/kg 50 group 100 group. Following pretreatment levamisole, or baicalin, challenged 1 × 10 8 CFU . Our results showed that modified routine blood indicators biochemical parameters; downregulated IL-1β, IL-10, IL-18, TNF-α IFN-γ mRNA expression; upregulated IL-2 IL-8 expression in blood. Baicalin, increased proportions CD3 + T cells, CD4 CD8 cells – CD21 B splenocyte population, blood, inhibited TIM-3 activation. reduced p-PI3K, p-Akt, p-mTOR expression, p-MEK1/2/MEK1/2 p-ERK1/2/ERK1/2 ratios RAS expression. provided substantial protection against challenge relieved tissue histopathological damage. findings might provide new strategies for controlling other immunosuppressive diseases.
Language: Английский
Citations
2
PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(10), P. e1012188 - e1012188
Published: Oct. 4, 2024
Mycobacterium tuberculosis (Mtb) infection induces a marked influx of neutrophils into the lungs, which intensifies severity (TB). The metabolic state significantly influences their functional response during inflammation and interaction with bacterial pathogens. However, effect Mtb on neutrophil metabolism its consequent role in TB pathogenesis remain unclear. In this study, we examined contribution glycolysis fatty acid responses to HN878 using ex-vivo assays murine models. We discover that blocking aggravates pathology, whereas inhibiting oxidation (FAO) yields protective outcomes, including reduced weight loss, immunopathology, burden lung. Intriguingly, FAO inhibition preferentially disrupts recruitment pathogen-permissive immature population (Ly6G lo/dim ), known accumulate TB. Targeting carnitine palmitoyl transferase 1a (Cpt1a)-a crucial enzyme mitochondrial β-oxidation-either through chemical or genetic methods impairs neutrophils’ ability migrate sites while also enhancing antimicrobial function. Our findings illuminate critical influence immunometabolism pathogenesis, suggesting manipulating presents novel avenue for host-directed therapies by modulating functions.
Language: Английский
Citations
2
Immunology, Journal Year: 2024, Volume and Issue: 173(2), P. 381 - 393
Published: July 14, 2024
Abstract Among several quantitative trait loci involved in tuberculosis (TB) control mice, one was mapped within the chromosome 17 segment occupied by H2 complex and another 3 comprising S100A8/9 genes, which encode neutrophil inflammatory factor S100A8/9. Previously, we developed a panel of ‐congenic mouse strains differing small segments major histocompatibility Class II (MHC‐II) region from TB‐susceptible j mice transferred onto genetic background TB‐resistant C57BL/6 ( b ) strain. Susceptible B6.I‐9.3 differ B6 progenitors alleles their only classical MHC‐II H2‐Aβ gene. The goals present study were to: (i) comprehensively characterise differences TB‐related phenotypes between two (ii) decipher interactions genes. Here, describe dynamics differentiating (colony forming units counts, histopathology, lung immune cell infiltration cytokine profiles). We show that disproportionally diminished CD4 + T‐cell population, an enlarged S100A8/9‐positive population higher serum levels collectively form ‘susceptible’ phenotype before infection. An increase IL‐17 decrease intrferon‐gamma production T‐cells these provide mechanistic explanation this phenotype. Using F2 segregation analysis, number S100A8/9‐producing neutrophils lungs spleens proportion Th17 are significantly lower presence dominant ‘resistant’ allele compared to recessive j/j genotype. This provides direct evidence MHC‐II‐regulated landscapes determine abundance infection, important pathogenic TB immunity.
Language: Английский
Citations
1
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: Nov. 7, 2024
Cytokine of interferon-gamma (IFNγ) plays a vital role in the immune response against Mycobacteria tuberculosis (Mtb) infection, yet specific function T cells producing IFNγ this process remains unclear. In study, we first isolated + CD3 induced by Mtb antigens using surface staining assays. which showed strong ability to inhibit growth intracellular mycobacteria macrophages. Peripheral blood mononuclear (PBMCs) from healthy individuals were then challenged with Bacillus Calmette–Guérin (BCG) or Mtb, respectively, sort IFNγ-secreting for mRNA sequencing analyze gene expression patterns. The results integrated data analysis revealed distinct patterns between BCG vaccine and those pathogens. Further, unlike Mtb-induced cells, BCG-induced expressed high levels interleukin-2 (IL-2), increased frequencies these production effector cytokines IL-2. Our findings suggested that IL-2 presented potent functions growth, while infection impaired cells.
Language: Английский
Citations
1
Advanced Biology, Journal Year: 2024, Volume and Issue: 8(10)
Published: July 8, 2024
Abstract Mycobacterium tuberculosis ( M. tb ) is a significant intracellular pathogen responsible for numerous infectious disease‐related deaths worldwide. It uses ESX‐1 T7SS to damage phagosomes and enter the cytosol of host cells after phagocytosis. During infection, mitochondria release dsDNA, which activates CGAS‐STING1 pathway. This pathway leads production type I interferons proinflammatory cytokines autophagy, targets degrades bacteria within autophagosomes. However, role IFNs in immunity against controversial. While previous research has suggested protective role, recent findings from cgas‐sting1 knockout mouse studies have contradicted this. Additionally, study using mice non‐human primate models uncovered new mechanism by neutrophils recruited lung infections form neutrophil extracellular traps. Activating plasmacytoid dendritic causes them produce IFNs, interfere with function interstitial macrophages increase likelihood tuberculosis. Notably, its virulence proteins disrupt signaling leading enhanced pathogenesis. Investigating can help develop ways fight
Language: Английский
Citations
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