Human milk oligosaccharides regulate human macrophage polarization and activation in response to Staphylococcus aureus

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июнь 6, 2024

Human milk oligosaccharides (HMOs) are present in high numbers of lactating women. They beneficial to gut health and the habitant microbiota, but less is known about their effect on cells from immune system. In this study, we investigated direct three structurally different HMOs human derived macrophages before challenge with Staphylococcus aureus ( S. ). The study demonstrates that individual HMO structures potently affect activation, differentiation development monocyte-derived response . 6´-Sialyllactose (6’SL) had most pronounced against , as illustrated by altered expression macrophage surface markers, pointing towards an activated M1-like macrophage-phenotype. Similarly, 6’SL increased production pro-inflammatory cytokines TNF-α, IL-6, IL-8, IFN-γ IL-1β, when exposing combination compared alone. Interestingly, treated exhibited proliferation profile classic M1 transcription factor NF-κB. also enhanced phagocytosis uptake Importantly, did not notably activation without exposure. Together, these findings show can augment causing inflammatory absence suggesting assist system targeting important pathogens during early infancy.

Язык: Английский

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From metabolic to epigenetic: Insight into trained macrophages in atherosclerosis (Review)

Molecular Medicine Reports, Год журнала: 2024, Номер 30(2)

Опубликована: Июнь 20, 2024

Atherosclerosis (AS) is a chronic inflammatory disease caused by the deposition of lipoproteins and sequent immune responses. Within atherosclerotic plaque, macrophages are most abundant cells play great part as protagonists promoters AS. In past decade, concept 'trained immunity' has emerged, which highlights memory characteristics innate immunity, thus opening up new avenue research. Evidence suggests that trained immunity may regulate onset progression AS with playing an important dynamic role in atherogenesis. The present review provided summary concepts related to its relationship Furthermore, different phenotypes responding various stimuli within plaque were presented, along complex mechanisms metabolic epigenetic reprogramming cells. Finally, several promising therapeutic approaches for cardiovascular discussed, shed light on clinical strategies.

Язык: Английский

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Evidence of innate training in bovine γδ T cells following subcutaneous BCG administration

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 18, 2024

The Bacillus Calmette Guerin (BCG) vaccine has been shown to induce non-specific protection against diseases other than tuberculosis in vaccinated individuals, attributed the induction of trained immunity. We have previously demonstrated that BCG administration induces innate immune training mixed peripheral blood mononuclear cells and monocytes calves. Gamma Delta (γδ) T are non-conventional exhibit adaptive system features. They higher proportion cattle humans or rodents play an essential role bovine response pathogens. In current study, we determined if induced γδ cells. A group 16 pre-weaned Holstein calves (2-4 d age) were enrolled study randomly assigned control groups (n=8/group). received two doses 10 6 colony forming units (CFU) Danish strain subcutaneously, separated by 2 weeks. remained unvaccinated. delta purified from using magnetic cell sorting three weeks after receiving 1 st dose. observed functional changes BCG-treated increased IL-6 TNF-α cytokine production vitro stimulation with Escherichia coli LPS PAM3CSK4. ATAC-Seq analysis 78,278 regions open chromatin (peaks) revealed had altered epigenetic status compared Differentially accessible peaks (DAP) found near promoters immunity-related genes like Siglec14 , Irf4 Ifna2 Lrrfip1 Tnfrsf10d 4-fold more MOTIF enrichment sequences within DAPs, which explores transcription factor binding motifs (TFBM) upstream regulatory elements, TFBM for Eomes IRF-5 among most enriched factors. GO proximal DAPs showed pathways such as regulation IL-2 production, T-cell receptor signaling pathway, pathways. conclusion, our shows subcutaneous can memory form immunity This is associated accessibility response-related genes, thereby inducing a evidenced production.

Язык: Английский

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Alcohol, HMGB1, and Innate Immune Signaling in the Brain

Alcohol research, Год журнала: 2024, Номер 44(1)

Опубликована: Янв. 1, 2024

Binge drinking (i.e., consuming enough alcohol to achieve a blood ethanol concentration of 80 mg/dL, approximately 4-5 drinks within 2 hours), particularly in early adolescence, can promote progressive increases and alcohol-related problems that develop into compulsive use the chronic relapsing disease, disorder (AUD). Over past decade, neuroimmune signaling has been discovered contribute alcohol-induced changes drinking, mood, neurodegeneration. This review presents mechanistic hypothesis supporting high mobility group box protein 1 (HMGB1) Toll-like receptor (TLR) as key elements across glia neurons, which shifts gene transcription synapses, altering neuronal networks development AUD. may help guide further research on prevention treatment.

Язык: Английский

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Peptidoglycan recognition protein PGRP-5 is involved in immune defence and neuro-behavioral disorders in zebrafish embryos

PLoS ONE, Год журнала: 2025, Номер 20(1), С. e0315714 - e0315714

Опубликована: Янв. 31, 2025

Peptidoglycan recognition proteins (PGRPs) are the evolutionarily highly conserved class of pattern receptors, however, their functions on innate immune system and neuro-inflammatory response in aquatic organism still poorly understood. In this study, we systematically investigated molecular PGRPs zebrafish embryos. Firstly, identified three phylogenetic analysis suggested that DrPGRP-5 was a novel member PGRP superfamily evolution. Secondly, endogenous mRNA levels were expressed brain muscle while significantly down-regulated liver egg at 72 hpf Thirdly, greatly elevated after 6 h E. coli infection but reached its highest value 24 M. luteus stimulation. Moreover, knock-down could reduce pro-inflammatory cytokines such as TNF-α, IL-1β IL-6, increased expression anti-inflammatory cytokine TGF-β. On other hand, locomotor behavior abilities antioxidant enzyme activities CAT SOD obviously decreased under KD conditions. Finally, incubation embryos with neuroprotective agents (10 μM Minocycline) can partially rescue DrPGRP5-regulated behavior. Taken together, our data PGRP-5 is involved defenses regulated neurobehavior neuro-inflammation, which may provide new strategies for treatment diseases organisms.

Язык: Английский

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