Functionally distinct T-helper cell phenotypes predict resistance to different types of parasites in a wild mammal

Abstract

The adaptive immune system is critical to an effective response to infection in vertebrates, with T-helper (Th) cells pivotal in orchestrating these responses. In natural populations where co-infections are the norm, different Th responses are likely to play an important role in maintaining host health and fitness, a relationship which remains poorly understood in wild animals. In this study, we characterised variation in functionally distinct Th responses in a wild population of Soay sheep by enumerating cells expressing Th-subset specific transcription factors and quantifying Th-associated cytokines. We tested the prediction that raised Th1 and Th2 responses should predict reduced apicomplexan and helminth parasite burdens, respectively. All measures of Th-associated cytokine production increased with age, while Th17- and regulatory Th-associated cytokine production increased more rapidly with age in males than females. Independent of age, sex, and each other, IL-4 and Gata3 negatively predicted gastro-intestinal nematode faecal egg count, while IFN-γ negatively predicted coccidian faecal oocyst count. Our results provide important support from outside the laboratory that Th1 and Th2 responses predict resistance to different kinds of parasites, and illustrate how harnessing specific reagents and tools from laboratory immunology will illuminate our understanding of host-parasite interactions in the wild.

Longitudinal dynamics of co-infecting gastrointestinal parasites in a wild sheep population

“…Furthermore, resistance to helminths is dependent on T helper type 2 (Th2) responses, which can be constrained by immune commitment to the Th1 responses required for resistance to microparasites such as coccidia (Graham, 2008 ). Recent evidence in wild Soay sheep has shown that Th1-associated immune phenotypes predicted reduced coccidian FOCs, while Th2-associated phenotypes predicted reduced strongyle FECs (Corripio-Miyar et al ., 2022 ). Although this supports the role of functionally distinct aspects of the immune response in controlling these two different parasite groups, we also found that sheep mounting strong Th1 responses also tended to mount strong Th2 responses (Corripio-Miyar et al 2022 ).…”

“…Recent evidence in wild Soay sheep has shown that Th1-associated immune phenotypes predicted reduced coccidian FOCs, while Th2-associated phenotypes predicted reduced strongyle FECs (Corripio-Miyar et al ., 2022 ). Although this supports the role of functionally distinct aspects of the immune response in controlling these two different parasite groups, we also found that sheep mounting strong Th1 responses also tended to mount strong Th2 responses (Corripio-Miyar et al 2022 ). It is possible that the immune responses that develop in sheep to coccidia during the first year of life are more effective than those against strongyle and that varied resource costs of anti-coccidian vs anti-strongyle responses may account for the varied effect of reproductive status on severity of infection.…”

Regulation of piglet T-cell immune responses by thioredoxin peroxidase from Cysticercus cellulosae excretory-secretory antigens

“…When stimulated by antigens, immature DCs recognize, uptake, and process antigens, and gradually mature in the process of migration. Mature DCs present antigens to naive CD4 + T cells through the major histocompatibility complex-II (MHC-II), thereby enabling CD4 + T cells to be activated and to differentiate into different cell subsets that secrete various cytokines, resulting in different types of adaptive immune responses, such as Th1, Th2, Th17, and Tregs (Letendre et al, 2018;Corripio-Miyar et al, 2022). Under normal circumstances, IFN-γ secreted by Th1 and IL-4 secreted by Th2 antagonize each other to maintain immune balance in the body.…”

The adaptive immune response toTrichurisin wild versus laboratory mice: An established model system in context

“…For wild non-model species, immunological analysis tools are often limited (5-7), and ethical considerations can limit study designs. Despite these difficulties, several studies have been performed recently to understand variation in T cell immune responses in wild mammals (8)(9)(10)(11)(12)(13). Further, pioneering studies have started to probe immune responses to parasite infection in M. m. domesticus in the wild (14) and laboratory mice released into outdoor enclosures (4).…”