Trained Immunity Enhances Host Resistance to Infection in Aged Mice.

Aging significantly increases the incidence and severity of infections, with individuals aged 65 and above accounting for 65% of sepsis cases. Innate immune training, known as "trained immunity" or "innate immune memory", has emerged as a potential strategy to enhance infection resistance by modulating the aging immune system. We investigated the impact of β-glucan-induced trained immunity on aged mice (18-20 months old) compared to young adult mice (10-12 weeks old).

A Randomized Controlled Trial of 2% Chlorhexidine Gluconate Skin Preparation Cloths for the Prevention of Surgical Site Infections in Adults Undergoing Spine Surgeries: Residual Reduction in Skin Bacterial Load for 4 Days.

Background: Surgical site infections (SSI) result in increased morbidity and mortality, prolonged recovery, longer hospital length of stay for medication or possible additional surgeries, and escalated health care costs. The purpose of this randomized controlled trial was to compare SSI rates and overall skin flora burden between those using chlorhexidine (CHG) cloths versus soap and water preoperatively in the adult spine surgery population.

Methods: Subjects were randomized preoperatively to use 2% CHG cloths versus soap and water the night before and morning of surgery prior to the operation.

Immunoresponsive Gene 1 Facilitates TLR4-agonist-Induced Augmentation of Innate Antimicrobial Immunity.

Treatment with the toll-like receptor (TLR) 4 agonist monophosphoryl lipid A (MPLA) conditions innate immunocytes to respond robustly to subsequent infection, a phenotype termed innate immune memory. Our published studies show that metabolic reprogramming of macrophages is a prominent feature of the memory phenotype. We undertook studies to define the functional contributions of tricarboxylic acid (TCA) cycle reprogramming to innate immune memory.

Weight loss-induced adipose macrophage memory improves local clearance in male mice.

Different stimuli can induce innate immune memory to improve pathogen defense or worsen cardiometabolic disease. However, it is less clear if the same stimuli can induce both the protective and detrimental effects of innate immune memory. We previously showed that weight loss induces innate immune memory in adipose macrophages that correlates with worsened diabetes risk after weight regain.

Improving Neuromuscular Monitoring Through Education-Based Interventions and Studying Its Association With Adverse Postoperative Outcomes: A Retrospective Observational Study.

Background: We assessed the association between education-based interventions, the frequency of train-of-four (TOF) monitoring, and postoperative outcomes.

Methods: We studied adults undergoing noncardiac surgery from February 1, 2020 through October 31, 2021. Our education-based interventions consisted of 3 phases.

Bacteria- and fungus-derived PAMPs induce innate immune memory via similar functional, metabolic, and transcriptional adaptations.

Exposure to pathogen-associated molecular patterns (PAMPs) induces an augmented, broad-spectrum antimicrobial response to subsequent infection, a phenomenon termed innate immune memory. This study examined the effects of treatment with β-glucan, a fungus-derived dectin-1 ligand, or monophosphoryl lipid A (MPLA), a bacteria-derived Toll-like receptor 4 ligand, on innate immune memory with a focus on identifying common cellular and molecular pathways activated by these diverse PAMPs. Treatment with either PAMP prepared the innate immune system to respond more robustly to Pseudomonas aeruginosa infection in vivo by facilitating mobilization of innate leukocytes into blood, recruitment of leukocytes to the site of infection, augmentation of microbial clearance, and attenuation of cytokine production.

Pretreatment with a novel Toll-like receptor 4 agonist attenuates renal ischemia-reperfusion injury.

Acute kidney injury (AKI) is common in surgical and critically ill patients. This study examined whether pretreatment with a novel Toll-like receptor 4 agonist attenuated ischemia-reperfusion injury (IRI)-induced AKI (IRI-AKI). We performed a blinded, randomized-controlled study in mice pretreated with 3-deacyl 6-acyl phosphorylated hexaacyl disaccharide (PHAD), a synthetic Toll-like receptor 4 agonist.

MyD88-dependent signaling drives toll-like receptor-induced trained immunity in macrophages.

Immunocompromised populations are highly vulnerable to developing life-threatening infections. Strategies to protect patients with weak immune responses are urgently needed. Employing trained immunity, whereby innate leukocytes undergo reprogramming upon exposure to a microbial product and respond more robustly to subsequent infection, is a promising approach.

INTRAPULMONARY TREATMENT WITH A NOVEL TLR4 AGONIST CONFERS PROTECTION AGAINST KLEBSIELLA PNEUMONIA.

Objectives: Nosocomial pneumonia is a common complication in critically ill patients. The goal of this study was to examine the efficacy of the Toll-like receptor 4 agonist 3-deacyl phosphorylated hexacyl disaccharide (3D PHAD), in a clinically relevant murine model of pneumonia, and assess the cellular mechanisms that mediate the protective response. Design: Mice received intrapulmonary 3D PHAD (20 μg) or vehicle for 2 consecutive days before challenge with intrapulmonary Klebsiella pneumoniae (2.

Trained Immunity Enhances Human Monocyte Function in Aging and Sepsis.

Aging plays a critical role in the incidence and severity of infection, with age emerging as an independent predictor of mortality in sepsis. Trained immunity reprograms immunocytes to respond more rapidly and effectively to pathogens and serves as a potential approach to improve immune function in aging and/or sepsis. However, there is very little data on trained immunity in the aging immune system or in the presence of sepsis.

Initial estuarine response to inorganic nutrient inputs from a legacy mining facility adjacent to Tampa Bay, Florida.

Legacy mining facilities pose significant risks to aquatic resources. From March 30th to April 9th, 2021, 814 million liters of phosphate mining wastewater and marine dredge water from the Piney Point facility were released into lower Tampa Bay (Florida, USA). This resulted in an estimated addition of 186 metric tons of total nitrogen, exceeding typical annual external nitrogen load estimates to lower Tampa Bay in a matter of days.

Innate Immune Memory and the Host Response to Infection.

Unlike the adaptive immune system, the innate immune system has classically been characterized as being devoid of memory functions. However, recent research shows that innate myeloid and lymphoid cells have the ability to retain memory of prior pathogen exposure and become primed to elicit a robust, broad-spectrum response to subsequent infection. This phenomenon has been termed innate immune memory or trained immunity.

β-Glucan Induces Distinct and Protective Innate Immune Memory in Differentiated Macrophages.

Bacterial infections are a common and deadly threat to vulnerable patients. Alternative strategies to fight infection are needed. β-Glucan, an immunomodulator derived from the fungal cell wall, provokes resistance to infection by inducing trained immunity, a phenomenon that persists for weeks to months.

Immune Checkpoints: Novel Therapeutic Targets to Attenuate Sepsis-Induced Immunosuppression.

Sepsis is a leading cause of death in intensive care units and survivors develop prolonged immunosuppression and a high incidence of recurrent infections. No definitive therapy exists to treat sepsis and physicians rely on supportive care including antibiotics, intravenous fluids, and vasopressors. With the rising incidence of antibiotic resistant microbes, it is becoming increasingly critical to discover novel therapeutics.

Trained immunity, tolerance, priming and differentiation: distinct immunological processes.

The similarities and differences between trained immunity and other immune processes are the subject of intense interrogation. Therefore, a consensus on the definition of trained immunity in both in vitro and in vivo settings, as well as in experimental models and human subjects, is necessary for advancing this field of research. Here we aim to establish a common framework that describes the experimental standards for defining trained immunity.

Reversal of sepsis-induced T cell dysfunction: OX-40 to the rescue?

The study of Unsinger and colleagues provide important insights into OX40 mediated immunotherapy as a potential approach for the treatment of sepsis induced immune suppression.

The Metabolic Basis of Immune Dysfunction Following Sepsis and Trauma.

Critically ill, severely injured and high-risk surgical patients are vulnerable to secondary infections during hospitalization and after hospital discharge. Studies show that the mitochondrial function and oxidative metabolism of monocytes and macrophages are impaired during sepsis. Alternatively, treatment with microbe-derived ligands, such as monophosphoryl lipid A (MPLA), peptidoglycan, or β-glucan, that interact with toll-like receptors and other pattern recognition receptors on leukocytes induces a state of innate immune memory that confers broad-spectrum resistance to infection with common hospital-acquired pathogens.

Monophosphoryl lipid A pretreatment suppresses sepsis- and LPS-induced proinflammatory cytokine production in the medullary thick ascending limb.

Sepsis is the leading cause of acute kidney injury in critically ill patients. Tumor necrosis factor-α (TNF-α) has been implicated in the pathogenesis of septic kidney injury; however, the sites and mechanisms of renal TNF-α production during sepsis remain to be defined. In the present study, we showed that TNF-α expression is increased in medullary thick ascending limbs (MTALs) of mice with sepsis induced by cecal ligation and puncture.

Social Factors Key to Landscape-Scale Coastal Restoration: Lessons Learned from Three U.S. Case Studies.

In the United States, extensive investments have been made to restore the ecological function and services of coastal marine habitats. Despite a growing body of science supporting coastal restoration, few studies have addressed the suite of societally enabling conditions that helped facilitate successful restoration and recovery efforts that occurred at meaningful ecological (i.e.

Assessment of the cumulative effects of restoration activities on water quality in Tampa Bay, Florida.

Habitat and water quality restoration projects are commonly used to enhance coastal resources or mitigate negative impacts of water quality stressors. Significant resources have been expended for restoration projects, yet much less attention has focused on evaluating broad regional outcomes beyond site-specific assessments. This study presents an empirical framework to evaluate multiple datasets in the Tampa Bay area (Florida, USA) to identify 1) the types of restoration projects that have produced the greatest improvements in water quality, and 2) over which time frames different projects may produce water quality benefits.

Immunobiology and application of toll-like receptor 4 agonists to augment host resistance to infection.

Infectious diseases remain a threat to critically ill patients, particularly with the rise of antibiotic-resistant bacteria. Septic shock carries a mortality of up to ∼40% with no compelling evidence of promising therapy to reduce morbidity or mortality. Septic shock survivors are also prone to nosocomial infections.

Phosphorylated Hexa-Acyl Disaccharides Augment Host Resistance Against Common Nosocomial Pathogens.

Objectives: To determine whether synthetic phosphorylated hexa-acyl disaccharides provide antimicrobial protection in clinically relevant models of bacterial infection.

Design: Laboratory study.

Setting: University laboratory.