Temperature sensitivity of bat antibodies links metabolic state with antigen-recognition diversity

Abstract

AbstractImmune system in bats features multiple unique properties that result in overall dampened inflammatory responses and increased tissue protection, explaining their tolerance to viral infections and unusually long lifespan. As heterothermic animals, bats exhibit large variations in body temperature on a daily and seasonal basis. In the present study, we demonstrated that temperature fluctuations corresponding to different physiological states in bats exert a dramatic impact on bat antibody repertoires. At temperatures typical for elevated metabolic activity during flight, IgG antibodies fromMyotis myotis(Borkhausen, 1797) andNyctalus noctula(Schreber, 1774) largely broaden their antigen binding diversity and affinity, recognizing both pathogen-derived and autoantigens. On the contrary, at temperatures reflecting inactive physiological states (torpor, hibernation), the breadth of immune diversity is substantially reduced. Importantly, temperature-dependent diversification of antibody specificities results in preferential recognition of damaged but not alive endothelial cells. This indicats that metabolism might influence not only pathogen recognition function but also anti-inflammatory functions of bat antibodies. Our mechanistic studies revealed particular molecular features of bat IgG, such as low thermodynamic stability and increased hydrophobicity, that can explain their distinctive behavior. This study reveals another facet of the enigmatic immune system of bats, extends our understanding of disease tolerance, highlights the link between metabolism and immunity, and might have important repercussions for human health.