A5045371886- Immune Response and Inflammation
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Sepsis Diagnosis and Treatment
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Long-Term Effects of COVID-19
- Vitamin C and Antioxidants Research
- Pancreatitis Pathology and Treatment
- Bacterial Identification and Susceptibility Testing
- Climate Change and Health Impacts
- Thermal Regulation in Medicine
- Endoplasmic Reticulum Stress and Disease
- Intensive Care Unit Cognitive Disorders
- Immunotherapy and Immune Responses
- Animal Virus Infections Studies
- Liver Disease Diagnosis and Treatment
University of Iowa
2020-2025
Abstract Human sepsis is a complex disease that manifests with diverse range of phenotypes and inherent variability among individuals, making it hard to develop comprehensive animal model. Despite this difficulty, numerous models have been developed capture many key aspects human sepsis. The robustness these vital for conducting pre‐clinical studies test potential therapeutics. In article, we describe four different murine can be used address scientific questions relevant the pathology...
Abstract Numerous models are available for the preclinical study of sepsis, and they fall into one three general categories: (1) administration exogenous toxins (e.g., lipopolysaccharide, zymosan), (2) virulent bacterial or viral challenge, (3) host barrier disruption, e.g., cecal ligation puncture (CLP) colon ascendens stent peritonitis (CASP). Of murine used to pathophysiology CLP combines tissue necrosis polymicrobial sepsis secondary autologous fecal leakage, as well hemodynamic...
Abstract Cancer prognosis often correlates with the number of tumor-infiltrating CD8 T cells, but many these cells recognize pathogens that commonly infect humans. The contribution pathogen-specific “bystander” to antitumor immunity remains largely unknown. Inflammatory cytokines are sufficient for memory cell activation and gain effector functions, indicating tumor-derived inflammation could facilitate participate in tumor control. In this study, we show contrast tumor-specific primary...
Abstract Establishing the magnitude and kinetics of polyclonal Ag-specific CD8 T-cell responses, in addition to their functional fitness, is critical for evaluating a host’s ability respond different kinds infections and/or immunizations. To track responses during infection, surrogate-activation-marker approach (CD8αloCD11ahi) used distinguish naïve Ag-experienced effector/memory T cells vivo. However, semidifferentiated virtual memory (Tvm) have recently been identified...
The dysregulated host response and organ damage following systemic infection that characterizes a septic event predisposes individuals to chronic immunoparalysis state associated with severe transient lymphopenia diminished lymphocyte function, thereby reducing long-term patient survival quality of life. Recently, we observed lasting production reactive oxygen species (ROS) in mice survive sepsis. ROS is potent mechanism for targeting infection, but excessive can prove maladaptive by causing...
Abstract Sepsis, an amplified immune response to systemic infection that leads life-threatening organ dysfunction, affects >125,000 people/day worldwide with 20% mortality. Modest therapeutic progress for sepsis has been made, in part because of the lack translatability between mouse-based experimental models and humans. One potential reason this difference stems from extensive use immunologically naive specific pathogen-free mice preclinical research. To address issue, we used...
Long-lasting sepsis-induced immunoparalysis has been principally studied in primary (1°) memory CD8 T cells; however, the impact of sepsis on cells with a history repeated cognate Ag encounters is largely unknown but important understanding role shaping pre-existing cell compartment. Higher-order are crucial providing immunity against common pathogens that reinfect host or generated by vaccination. In this study, we analyzed peripheral blood from septic patients and show defined specificity...
Sepsis, an amplified immune response to systemic infection, is characterized by a transient cytokine storm followed chronic dysfunction. Consequently, sepsis survivors are highly susceptible newly introduced infections, suggesting can influence the function and composition of naïve CD8 T cell pool resulting pathogen-induced primary responses. Here, we explored extent which induces phenotypic functional changes within pool. To interrogate this, cecal ligation puncture (CLP) mouse model...
Abstract Patients infected with SARS-CoV-2 experience variable disease susceptibility, and patients comorbidities such as sepsis are often hospitalized for COVID-19 complications. However, the extent to which initial infectious inoculum dose determines outcomes whether this can be used immunological priming in a genetically susceptible host has not been completely defined. We an established SARS-like murine model responses primary and/or secondary challenges hepatitis virus type 1 (MHV-1)...
SUMMARY Metabolic reprogramming in response to infection plays a critical role for septic survival. During episode, the heart heavily relies on hepatic lipid particles prevent damage and failure. Inositol- Requiring Enzyme 1 (IRE1) is most conserved unfolded protein (UPR) regulator that governs homeostasis of endoplasmic reticulum (ER), major site synthesis processing. Here we show hepatocyte IRE1 indispensable protecting against mortality two different rodent models experimental sepsis. The...
Abstract Patients infected with SARS-CoV-2 can experience variable susceptibility and sepsis-like immune dysfunction. Also, patients comorbidities such as previous septic events are more likely to be hospitalized succumb COVID19 complications. However, the extent which respiratory beta-coronavirus pathology is dose dependent produces dysregulation in an experimental murine model not completely defined. We utilized established SARS-like by infecting Murine Hepatitis Virus 1 (MHV-1)...