Publications by authors named "J R Bohannon"

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).

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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.

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Article Synopsis
  • Clostridioides difficile (C. diff) is a germ that causes diarrhea and serious gut problems, especially in hospitals.
  • It produces harmful proteins called toxins, including the less understood CDT toxin, which causes inflammation in the body.
  • Researchers found that CDT activates certain immune cells in a way that doesn't depend on a specific inflammatory pathway, suggesting its effects may not be as straightforward as previously thought.
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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.

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Article Synopsis
  • The August 2023 article in Science Signaling critiques the traditional macrophage classifications (M1/M2) by showing how transforming growth factor β (TGF-β) alters macrophage metabolism and function, leading to an unexpected phenotype.
  • TGF-β-treated macrophages increase glycolysis, decrease pro-inflammatory cytokines, and elevate coagulation factors, indicating a complex role in inflammation and metabolism during conditions like sepsis.
  • The study connects TGF-β's effects to COVID-19, showing similar metabolic changes in macrophages and suggesting that targeting TGF-β could be a therapeutic strategy for diseases characterized by uncontrolled inflammation and coagulation issues.
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