Frontiers in immunology
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Frontiers in immunology · Jan 2018
Intestinal Microbiota at Engraftment Influence Acute Graft-Versus-Host Disease via the Treg/Th17 Balance in Allo-HSCT Recipients.
Animal models have indicated that intestinal microbiota influence acute graft-versus-host disease (aGVHD) by modulating immune homeostasis. But, in humans, the mechanism by which the microbiota induces aGVHD remains unclear. In this study, we investigated the relationship between the intestinal microbiota and T cell subsets in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) to explore the mechanism by which microbiota induced aGVHD. ⋯ The level of acetylated H3 in CD4+ T cells was not only correlated with Lachnospiraceae/Ruminococcaceae, but also with the Treg/Th17 ratio (r = 0.354; p = 0.001). In conclusions, our results suggest that decreased Lachnospiraceae and Ruminococcaceae and increased Enterobacteriaceae, correlate with a Treg/Th17 imbalance, which might be through acetylated H3 in CD4+ T cells. These findings suggest that intestinal microbiota might induce aGVHD by influencing the Treg/Th17 balance.
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Frontiers in immunology · Jan 2018
A Label-Free Quantitative Proteomic Analysis of Mouse Neutrophil Extracellular Trap Formation Induced by Streptococcus suis or Phorbol Myristate Acetate (PMA).
Streptococcus suis (S. suis) ranks among the five most important porcine pathogens worldwide and occasionally threatens human health, particularly in people who come into close contact with pigs or pork products. An S. suis infection induces the formation of neutrophil extracellular traps (NETs) in vitro and in vivo, and the NET structure plays an essential role in S. suis clearance. However, the signaling pathway by which S. suis induces NET formation remains to be elucidated. ⋯ Of these peptidases, MMP-8 expression was obviously decreased in response to PMA, but it was not significantly changed in response to S. suis. A subsequent study further confirmed that MMP-8 activity was inversely correlated with NET formation induced by both stimuli. Therefore, the present study provides potentially important information about the manner by which neutrophils responded to the inducers to form NETs.
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Frontiers in immunology · Jan 2018
ReviewTherapeutic Potential of the Gut Microbiota in the Prevention and Treatment of Sepsis.
Alongside advances in understanding the pathophysiology of sepsis, there have been tremendous strides in understanding the pervasive role of the gut microbiota in systemic host resistance. In pre-clinical models, a diverse and balanced gut microbiota enhances host immunity to both enteric and systemic pathogens. Disturbance of this balance increases susceptibility to sepsis and sepsis-related organ dysfunction, while restoration of the gut microbiome is protective. ⋯ Modulation of the microbiota consists of either resupplying the pool of beneficial microbes by administration of probiotics, improving the intestinal microenvironment to enhance the growth of beneficial species by dietary interventions and prebiotics, or by totally recolonizing the gut with a fecal microbiota transplantation (FMT). We propose that there are three potential opportunities to utilize these treatment modalities over the course of sepsis: to decrease sepsis incidence, to improve sepsis outcome, and to decrease late mortality after sepsis. Exploring these three avenues will provide insight into how disturbances of the microbiota can predispose to, or even perpetuate the dysregulated immune response associated with this syndrome, which in turn could be associated with improved sepsis management.
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Frontiers in immunology · Jan 2018
Effects of Changes in the Levels of Damage-Associated Molecular Patterns Following Continuous Veno-Venous Hemofiltration Therapy on Outcomes in Acute Kidney Injury Patients With Sepsis.
Background: We investigated the association of damage-associated molecular pattern (DAMP) removal with mortality in sepsis patients undergoing continuous veno-venous hemofiltration (CVVH). Methods: Circulating levels of DAMPs [mitochondrial DNA (mtDNA); nuclear DNA (nDNA); heat shock protein 70 (HSP70); and high mobility group box 1 (HMGB1)] and cytokines were measured at baseline, 6 and 12 h after initiation of CVVH. Urinary DNA levels were analyzed at baseline and end of CVVH. ⋯ The urinary nDNA (β-globin) level before CVVH was an independent risk factor for the duration of CVVH in patients with sepsis (sRE = 0.460, 95% CI: 1.720-8.857, P = 0.005). Conclusion: CVVH removes inflammatory factors, reduces urinary DAMPs, and removes plasma DAMPs. However, survival decreases in response to higher HSP70 clearance.
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Frontiers in immunology · Jan 2018
Functional Heterogeneity of CD4+ Tumor-Infiltrating Lymphocytes With a Resident Memory Phenotype in NSCLC.
Resident memory T cells (TRM) inhabit peripheral tissues and are critical for protection against localized infections. Recently, it has become evident that CD103+ TRM are not only important in combating secondary infections, but also for the elimination of tumor cells. In several solid cancers, intratumoral CD103+CD8+ tumor infiltrating lymphocytes (TILs), with TRM properties, are a positive prognostic marker. ⋯ Furthermore, a large proportion of TILs expressed co-stimulatory receptors CD27 and CD28, unlike lung TRM, suggesting a less differentiated phenotype. Agonistic triggering of these receptors improved cytokine production of CD103+CD4+ and CD69+CD8+ TILs. Our findings thus provide a rationale to target CD103+CD4+ TILs and add co-stimulation to current therapies to improve the efficacy of immunotherapies and cancer vaccines.