Urinary neopterin of wild chimpanzees indicates that cell-mediated immune activity varies by age, sex, and female reproductive status

Abstract

The study of free-living animal populations is necessary to understand life history trade-offs associated with immune investment. To investigate the role of life history strategies in shaping proinflammatory cell-mediated immune function, we analyzed age, sex, and reproductive status as predictors of urinary neopterin in 70 sexually mature chimpanzees (Pan troglodytes) at Ngogo, Kibale National Park, Uganda. In the absence of clinical signs of acute infectious disease, neopterin levels significantly increased with age in both male and female chimpanzees, as observed in humans and several other vertebrate species. Furthermore, males exhibited higher neopterin levels than females across adulthood. Finally, females with full sexual swellings, pregnant females, and post-reproductive females, the oldest individuals in our sample, exhibited higher neopterin levels than lactating females and cycling females without full swellings. Variation in females’ neopterin levels by reproductive status is consistent with post-ovulatory and pregnancy-related immune patterns documented in humans. Together, our results provide evidence of ample variation in chimpanzee immune activity corresponding to biodemographic and physiological variation. Future studies comparing immune activity across ecological conditions and social systems are essential for understanding the life histories of primates and other mammals.

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

“…Previous studies have found a large degree of variability in baseline neopterin in humans ( 53 ) and primates [barbary macaques, ( 24 ); chimpanzees, ( 18 , 19 , 21 , 22 ); bonobos, ( 23 ); emperor tamarins, ( 26 ); saddle-back tamarins, ( 26 )], making it difficult to determine “normal”, baseline neopterin values for primate species. Importantly, there is overlap between baseline neopterin and neopterin after immune activation.…”

“…In line with previous research, we found that both creatinine and specific gravity (SG) were tightly correlated (36,37) suggesting that either can be used to standardize urinary neopterin. Some wild primate urinary neopterin studies used SG to control for urine dilution, most likely because it is a more field-friendly and economical method to control for sample concentration than creatinine assays (18,19,(21)(22)(23)(24)26). We now know SG is a sufficient method to control for urine dilution for neopterin analysis in capuchin monkeys.…”

“…Given this, we predicted that neopterin would be elevated in wild compared to captive individuals. Lastly, a common pattern among primates, and humans, is that neopterin changes with age, specifically, it is high in infants, decreases through juvenile and early adulthood, and then increases again with advanced age ( 18 , 21 , 23 , 44 – 46 ). Thus, we predicted a similar pattern in both our wild and captive populations.…”

“…Neopterin has been used in clinical applications to monitor disease progression in humans (14) and has been found to increase in urine after HIV infection in macaque species (15)(16)(17) and respiratory infection in bonobos and chimpanzees (18,19). Urinary neopterin has been validated and integrated into health monitoring studies in a number of primate species (Pan troglodytes [chimpanzees; (18)(19)(20)(21)(22)], Pan paniscus [bonobos; (18,23)], Macaca sylvanus [barbary macaques; (24)] and has been shown to vary with age (18,23,24), differ between environments [captivity vs. wild; (20)], and respond to infection (18,19).…”

Female reproduction and viral infection in a long‐lived mammal

“…However, long‐term data also suggest that reproductive status does not predict the occurrence of clinically observable respiratory disease (Emery Thompson et al, 2018). Also, some but not all chimpanzees (González et al, 2020) exhibit higher levels of neopterin with age (Negrey et al, 2021), and high‐fertility females in some populations experience less of an age‐related increase in parasite loads than low‐fertility females (Phillips et al, 2020). Finally, in contrast with helminthic parasites, Plasmodium detection rates decrease with age, presumably due to acquired immunity (De Nys et al, 2014).…”