Abstract 15894: Adaptations of Innate Immunity in Hibernation: Mechanisms for Protection Against Acute Organ Injury

Abstract

Introduction: Hibernation is a natural molecular adaptation to extreme environmental conditions with important implications for perioperative organ protection. Hypothesis: We hypothesized that the hibernator cardioprotective phenotype is accompanied by altered expression of innate immune pattern-recognition receptors (PRRs) and inflammatory pathways. Methods: LV myocardium, peripheral blood monocytes (PBMC), and plasma were collected from rat, summer AGS, and winter AGS after sham, 3h or 24h ischemia/reperfusion (I/R). Results: Plasma troponin I detection confirmed greater I/R injury in rat compared to AGS (Fig 1). Proteomic profiling of LV myocardium detected multiple differences including higher expression of MyD88 dependent toll-like receptors (TLR) in rat compared to AGS; average levels of TLRs were 1.8 fold higher in rat compared with hibernating AGS. Comparison of PBMCs from rat, summer, and hibernating AGS revealed increased PRR expression and cytokine production in the rat compared to the AGS, along the TLR3/TICAM (Fig2), TLR/MyD88, and AIM2/inflammasome axes. Conclusions: Compared to AGS, rats experience robust inflammasome activation in response to I/R as evidenced by >30-fold increases in AIM2 and Caspase 1. Hibernation state differences in innate immunity exist, including reduced expression of PRRs(TLR1,3, and AIM2); additionally signaling via TLR 3 and 4 is greatly dampened in winter AGS due to nearly absent expression of TICAM1. Circulating immune effector cells in winter AGS have an abrogated response to DAMPs compared to cells from summer AGS or rat, as evidenced by reduced cytokine production.