Collaborative Research: Scaling of neutrophil functions in terrestrial mammals

This project investigates how antimicrobial functions of immune cells compensate or adjust to body mass in small vs. large mammalian hosts. Host body mass should shape immune defenses because it likely affects aspects of pathogen exposure, detection, and defense activation. Neutrophils are innate antimicrobial cells critical to the outcome of infections in mammals.

Although elephants have disproportionately more neutrophils than mice given their relative body masses, it is unknown whether an elephant’s neutrophil provides the same defenses as a mouse’s during a bacterial challenge. How neutrophil antibacterial responses and associated gene expression and energetics are related to an animal’s body mass will be investigated in terrestrial mammals with body masses spanning a range from a few grams (such as a mouse) to several hundred kilograms (such as an elephant).

Such a broad understanding of mammalian neutrophil functions can enhance disease-spread models by providing predictions about the level of immune defense expected in species never before studied. Participants will develop museum displays for a local museum of science and technology in Syracuse, NY, that collaborates in educational activities for every 8th-grader in the diverse Syracuse City school district, exposing students from groups underrepresented in STEM to science at a critical age.

The team will also teach local middle-school students to use microscopes in scientific inquiry. These activities will demonstrate how comparative research is important for understanding human and animal physiology and health.

This research project tests specific hypotheses about how neutrophil antibacterial responses vary with body mass. Previous studies raise the question whether a disproportionately greater neutrophil concentration in large mammals conveys additional immune protection or compensates for less effective killing by a single neutrophil. Specifically, the team will assess how neutrophil antibacterial functions change with body mass in 20 species of terrestrial mammals spanning 7 orders of magnitude in size.

The neutrophil activities to be characterized include direct killing, phagocytosis, metabolic changes and reactive oxygen species generation, and neutrophil extracellular traps and associated changes in gene expression. How the metabolic rates of neutrophil extracellular traps change with body mass in neutrophils from 11 species of primates spanning 5 orders of magnitude in size will also be measured.

Immune defenses will be quantified against a strain of Escherichia coli, a ubiquitous, zoonotic pathogen that poses a serious threat to industrial agriculture and human and non-human animals, including wildlife, proximal to these production sites. The team’s work addresses two Grand Challenges in Organismal Biology – how genomes become phenomes and how organisms maintain stability through change – and will advance understanding how body size constrains the evolution of innate immune defense processes in vertebrates.

Through an unprecedented comparative approach, the research promises to transform how scientists think about host-parasite interactions. The project will make available transcriptomic data and a database of images of neutrophil defenses that could be valuable for other systems biology and immune defense studies. In addition, training of postdoctoral fellows and undergraduate and graduate students across the three collaborating institutions will contribute to workforce development.

This award was co-funded by the BIO-IOS-Physiological Mechanisms and Biomechanics Program and the Symbiosis, Infection, and Immunity Program.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.