Validating Urinary Neopterin as a Biomarker of Immune Response in Captive and Wild Capuchin Monkeys

Abstract

Non-invasive health monitoring is advantageous for wild and captive primate populations because it reduces the need for traditional invasive techniques (i.e., anesthetization) that can be stressful and potentially harmful for individuals. The biomarker neopterin is an emerging tool in primatology to measure immune activation and immunosenescence, however, most neopterin studies have focused on catarrhine species with little comparative work examining neopterin and health in platyrrhines. To address this gap, we validated a commercially available enzyme-linked immunosorbent assay (ELISA) to measure urinary neopterin in two types of capuchin monkeys, a wild population of white-faced capuchins (Cebus imitator) and a socially housed captive colony of tufted capuchins (Sapajus apella). We analytically validated methods for measuring urinary neopterin in two capuchin populations and demonstrated that two commonly-used methods to control for urine concentration—creatinine and specific gravity (SG)—produced highly concordant results. We also biologically validated these methods by examining variation in neopterin levels based on environment (captive and wild) and age, and changes in levels associated with immune-response. We found that neopterin increased after immune perturbation (rabies vaccine booster), varied by environmental condition, and mirrored expected trends in immune system ontogeny. Our results improve understanding of the innate immune system in platyrrhine species and suggest neopterin may be useful for non-invasive health monitoring in both captive and wild primates.

Urinary neopterin reflects immunological variation associated with age, helminth parasitism, and the microbiome in a wild primate

“…The U-shaped association between age and neopterin in geladas recapitulates the pattern found in humans 23 , free-ranging mandrills 19 , and capuchins 24 , and is consistent with the patterns found in other studies that sampled from only one end of the age distribution 14 , 16 – 18 . High neopterin levels in infancy likely reflect the immune system’s first encounters with pathogens and parasites during the development of both innate and adaptive immune responses 53 – 55 , and high neopterin levels in old age likely arise from increased production of pro-inflammatory cytokines (including IFN-y, which stimulates neopterin-producing pathways) during senescence 53 .…”

“…High neopterin levels in adults may capture the chronic inflammation that accompanies chronological aging 21 , while high neopterin levels in infants may capture the T-cell helper (Th) 2-polarization of the developing immune system 22 . Studies that sampled humans, semi-wild mandrills, and captive and wild capuchins across the lifespan found a U-shaped relationship between neopterin and age, with the highest neopterin in the youngest and oldest individuals 19 , 23 , 24 . Concordantly, studies that sampled only adults found the highest neopterin in older individuals 16 , 18 and those that sampled only non-adults found the highest neopterin in younger individuals 12 , 14 .…”