Scaling of Antibacterial Immune Defenses in Mammals

Abstract

Terrestrial mammals span 7 orders of magnitude in body size, ranging from the < 2 g pygmy shrew (Suncus etruscus) to the > 3900 kg African elephant (Loxodonta africana). Although body size profoundly affects the behavior, physiology, ecology, and evolution of species, how investment in immune defenses changes with body size across species is unknown. Comparative immunology studies are often limited because of reagents or because assays are calibrated for a specific species. We developed a novel 12‐point dilution‐curve approach to compare complement‐mediated antibacterial capacity against 3 diverse bacterial species (Escherichia coli, Salmonella enterica, Micrococcus luteus) among >160 terrestrial species of mammals. We tested published predictions about the scaling of immune defenses, focusing on the Safety Factor Hypothesis, which predicts that broad, early‐acting immune defense should scale hypermetrically with body mass. Multivariate linear mixed models using Markov chain Monte Carlo techniques demonstrate that antibacterial activity across mammals exhibited isometry (scaling coefficient = 0), regardless of the bacterial species used in the challenge. For example, the antibacterial ability of a specific dilution scaled isometrically when serum was tested against E. coli(b95% Credible Intervals =‐0.144 : 0.044), S. enterica (b = ‐0.102 : 0.061), and M, luteus (b = ‐0.401 : 0.177). Therefore, body size was unrelated to killing capacity across species. Intriguingly, these results indicate that the serum of large mammals was less hospitable to bacteria than would be predicted by their metabolic rates. That is, if metabolic rates restrict the rate of organismal reactions as postulated by the Rate of Metabolism Hypothesis, large species should have disproportionately lower antibacterial capacity than small species, but they do not. These results have direct implications for effectively modeling the evolution of immune defenses and identifying potential reservoir hosts of zoonotic pathogens. This work was supported by the National Science Foundation (award numbers IOS 1656551 to C.J.D. and IOS 1656618 to L.B.M), and the authors have no competing interests to declare.