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The interaction between the Candida albicans cell wall and pattern recognition receptors is crucial for the initiation of host immune responses, which, ultimately, contribute to the clearance of this pathogenic fungus. In the present study, we investigate the ability of C. albicans mannans to modulate immune response and induce innate immune memory (also termed trained immunity). Using mutants of C. albicans that are defective in or lack mannosyl residues, we show that alterations in the mannosylation of the C. albicans cell wall affect the innate cytokine response and strongly reduce the secretion of T-cell–derived cytokines. Subsequently, we demonstrate that the branching of N -linked mannan, but not O -linked mannan, is essential to potentiate the induction of trained immunity, a process mediated by dectin 2. In conclusion, N -linked mannan is needed, in addition to β-glucans, for an effective induction of trained immunity by C. albicans. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness of low intra‐abdominal pressure (IAP) facilitated by deep neuromuscular block (NMB) to standard practice in improving the quality of recovery, preserving immune function, and enhancing parietal perfusion during robot‐assisted radical prostatectomy (RARP). Patients and Methods: In this blinded, randomised controlled trial, 96 patients were randomised to the experimental group with low IAP (8 mmHg) facilitated by deep NMB (post‐tetanic count 1–2) or the control group with standard IAP (14 mmHg) and moderate NMB (train‐of‐four 1–2). Recovery was measured using the 40‐item Quality of Recovery questionnaire and 36‐item Short‐Form Health survey. Immune function was evaluated by plasma damage‐associated molecular patterns, cytokines, and ex vivo lipopolysaccharide‐stimulated cytokine production. Parietal peritoneum perfusion was measured by analysing the recordings of indocyanine‐green injection. Results: Quality of recovery was not superior in the experimental group (n = 46) compared to the control group (n = 50). All clinical outcomes, including pain scores, postoperative nausea and vomiting, and hospital stay were similar. There were no significant differences in postoperative plasma concentrations of damage‐associated molecular patterns, cytokines, and ex vivo cytokine production capacity. The use of low IAP resulted in better parietal peritoneum perfusion. Conclusion: Despite better perfusion of the parietal peritoneum, low IAP facilitated by deep NMB did not improve the quality of recovery or preserve immune function compared to standard practice in patients undergoing RARP. [ABSTRACT FROM AUTHOR]

Background: Colorectal surgery is associated with moderate-to-severe postoperative complications in over 25% of patients, predominantly infections. Monocyte epigenetic alterations leading to immune tolerance could explain postoperative increased susceptibility to infections. This research explores whether changes in monocyte DNA accessibility contribute to postoperative innate immune dysregulation., Methods: Damage-associated molecular patterns (DAMPs) and ex vivo cytokine production capacity were measured in a randomized controlled trial (n = 100) in colorectal surgery patients, with additional exploratory subgroup proteomic (proximity extension assay; Olink) and epigenomic analyses (Assay for Transposase-Accessible Chromatin [ATAC sequencing]). Monocytes of healthy volunteers were used to study the effect of high-mobility group box 1 (HMGB1) and heat shock protein 70 (HSP70) on cytokine production capacity in vitro., Results: Plasma DAMPs were increased after surgery. HMGB1 showed a mean 235% increase from before- (preop) to the end of surgery (95% confidence interval [CI] [166 - 305], P < .0001) and 90% increase (95% CI [63-118], P = .0004) preop to postoperative day 1 (POD1). HSP70 increased by a mean 12% from preop to the end of surgery (95% CI [3-21], not significant) and 30% to POD1 (95% CI [18-41], P < .0001). Nuclear deoxyribonucleic acid (nDNA) increases by 66% (95% CI [40-92], P < .0001) at the end of surgery and 94% on POD1 (95% CI [60-127], P < .0001). Mitochondrial DNA (mtDNA) increases by 370% at the end of surgery (95% CI [225-515], P < .0001) and by 503% on POD1 (95% CI [332-673], P < .0001). In vitro incubation of monocytes with HSP70 decreased cytokine production capacity of tumor necrosis factor (TNF) by 46% (95% CI [29-64], P < .0001), IL-6 by 22% (95% CI [12-32], P = .0004) and IL-10 by 19% (95% CI [12-26], P = .0015). In vitro incubation with HMGB1 decreased cytokine production capacity of TNF by 34% (95% CI [3-65], P = .0003), interleukin 1β (IL-1β) by 24% (95% CI [16-32], P < .0001), and IL-10 by 40% (95% CI [21-58], P = .0009). Analysis of the inflammatory proteome alongside epigenetic shifts in monocytes indicated significant changes in gene accessibility, particularly in inflammatory markers such as CXCL8 (IL-8), IL-6, and interferon-gamma (IFN-γ). A significant enrichment of interferon regulatory factors (IRFs) was found in loci exhibiting decreased accessibility, whereas enrichment of activating protein-1 (AP-1) family motifs was found in loci with increased accessibility., Conclusions: These findings illuminate the complex epigenetic modulation influencing monocytes' response to surgical stress, shedding light on potential biomarkers for immune dysregulation. Our results advocate for further research into the role of anesthesia in these molecular pathways and the development of personalized interventions to mitigate immune dysfunction after surgery., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)