American Society of Naturalists

Cynthia J. Downs, Ned A. Dochtermann, Ray Ball, Kirk C. Klasing, and Lynn B. Martin (Jan 2020)

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Neutrophils increase disproportionately with body mass. An elephant’s immune system isn’t a mouse’s writ large

Super-sized surveillance – body size shapes mammal immune defenses

What species is better at fighting an infection, a mouse or an elephant? Body size is one of the most noticeable differences among species, but relationships between immune defenses and body size have largely been unstudied. Drs. Cynthia Downs (Hamilton College, currently at State University of New York, College of Environmental Science and Forestry), Ned Dochtermann (North Dakota State University), Kirk Klasing (University of California, Davis), Ray Ball (Eckerd College), and Lynn (Marty) Martin (University of South Florida) investigated whether body mass was related to concentrations of two important immune cell types in the blood among 100s of species of mammals ranging from tiny Jamaican fruit bats (~40 g) to giant killer whales (~5,600 kg). The researchers found that concentrations of lymphocytes, one type of white blood cell, didn’t change in any special way with body size. That is, a mouse and an elephant have the same number of lymphocytes per ml of blood. In contrast, big mammals had far, far more neutrophils in circulation than small species. Neutrophils are involved in early immune responses to many different kinds of invaders including bacteria and even bigger parasites such as worms. The researchers speculate that larger mammals might need so many more circulating neutrophils to overcome the inherent advantage that infectious agents have over the animals they infect. This advantage arises because small things replicate their cells much faster than big things; to offset this benefit of being small, big things keep around a large pool of nasty cells to attack invaders.

Altogether, this work shows that for some types of immune defenses, large and small mammals are fundamentally different. This insight could help us develop better ways to link results from lab mice to improvements of human health as well as enable us to make predictions about the immune systems of species never before studied. These data could also even help wildlife managers predict how good a species could be as a host for a newly emerging disease. This work was funded by National Science Foundation grant numbers 0947177, 1257773, 656618, 165655.

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Abstract

Theory predicts that body mass should affect the way organisms evolve and use immune defenses. We investigated the relationship between body mass and blood neutrophil and lymphocyte concentrations among 250+ terrestrial mammalian species. We tested whether existing theories (e.g., Protecton Theory, immune system complexity, and rate of metabolism) accurately predicted the scaling of immune cell concentrations. We also evaluated the predictive power of body mass for these leukocyte concentrations compared to sociality, diet, life history, and phylogenetic relatedness. Phylogeny explained >70% of variation in both lymphocytes and neutrophils, and body mass appeared more informative than other interspecific trait variation. In the best-fit mass-only model, neutrophils scaled hypermetrically (b = 0.11) with body mass whereas lymphocytes scaled isometrically. Extrapolating to total cell numbers, this exponent means that an African elephant circulates 13.3 million times the neutrophils of a house mouse, whereas their masses differ by only 250k-fold. We hypothesize that such high neutrophil numbers might offset the i) higher overall parasite exposure that large animals face and/or ii) the higher relative replication capacities of pathogens to host cells.