Transmissible cancer influences immune gene expression in an endangered marsupial, the Tasmanian devil (Sarcophilus harrisii)

Abstract

Understanding the effects of wildlife diseases on populations requires insight into local environmental conditions, host defence mechanisms, host life‐history trade‐offs, pathogen population dynamics, and their interactions. The survival of Tasmanian devils (Sarcophilus harrisii) is challenged by a novel, fitness limiting pathogen, Tasmanian devil facial tumour disease (DFTD), a clonally transmissible, contagious cancer. In order to understand the devils’ capacity to respond to DFTD, it is crucial to gain information on factors influencing the devils’ immune system. By using RT‐qPCR, we investigated how DFTD infection in association with intrinsic (sex and age) and environmental (season) factors influences the expression of 10 immune genes in Tasmanian devil blood. Our study showed that the expression of immune genes (both innate and adaptive) differed across seasons, a pattern that was altered when infected with DFTD. The expression of immunogbulins IgE and IgM:IgG showed downregulation in colder months in DFTD infected animals. We also observed strong positive association between the expression of an innate immune gene, CD16, and DFTD infection. Our results demonstrate that sampling across seasons, age groups and environmental conditions are beneficial when deciphering the complex ecoevolutionary interactions of not only conventional host‐parasite systems, but also of host and diseases with high mortality rates, such as transmissible cancers.

Understanding the evolution of immune genes in jawed vertebrates

“…So devils that breed younger, invest more into a single breeding season or tolerate the tumours for longer periods are able to contribute more to the next generation (Lachish et al, 2009 ; Wells et al, 2017 ). Within a few generations there have been allele frequency changes (detected using SNPs) in genomic areas surrounding immune‐ and cancer‐related genes (including CD146, THY1, CRBN; Epstein et al, 2016 ; Hubert et al, 2018 ; Stahlke et al, 2021 ), a reduction in alleles associated with abiotic local adaptation (Fraik et al, 2020 ) and even changes in gene expression with DFTD infection (immunoglobulins, NKG2D, CD16; Raven et al, 2022 ; Ujvari et al, 2016 ). The PAX3 gene has been associated with documented tumour regressions, possibly involved in a regulatory pathway, slowing tumour growth (Wright et al, 2017 ).…”

Integrating telomere biology into the ecology and evolution of natural populations: progress and prospects

“…Altogether, elucidating the ecology of gene expression and epigenetics in telomere maintenance across natural populations should therefore be considered an important task for the future. Raven et al (2022) discuss what is known about cancer and telomeres in the wild, a topic of considerable interest since telomeres have historically been studied in the context of cancer, with somatic down-regulation of telomerase postulated as a tumour protection mechanism in large bodies/long lived species. Telomerase activation has been identified as critical mutations that are associated with malignant cells.…”

“…Telomerase activation has been identified as critical mutations that are associated with malignant cells. Raven et al (2022) emphasize that telomere-cancer dynamics constitute a complex and a multifaceted process, in part because in humans both (too) long and (too) short telomeres can be associated with an increased cancer risk. Whether similar effects can be observed in natural populations of other species remains to be seen.…”

Complex associations between cancer progression and immune gene expression reveals early influence of transmissible cancer on Tasmanian devils

“…Tasmanian devil responses to DFTD infection are complex, with no differences between the transcriptomes of healthy and DFTD infected animals detected in lip tissue ( 20 ). However, more targeted analysis from blood has shown shifts in immune gene expression with DFTD infection ( 21 ). Innate immune gene expression (particularly CD16) increased, and some genes associated with adaptive immune function were downregulated with DFTD infection ( 21 ).…”

“…However, more targeted analysis from blood has shown shifts in immune gene expression with DFTD infection ( 21 ). Innate immune gene expression (particularly CD16) increased, and some genes associated with adaptive immune function were downregulated with DFTD infection ( 21 ). Targeted sequencing also showed a decline in T-cell receptor diversity and restricted T-cell clonal expansion ( 22 ).…”