Relationships between immune gene expression and circulating cytokine levels in wild house mice

Abstract

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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

“…However, contrary to our predictions, we found positive rather than negative associations between Th1-and Th2-associated measures. This provides rare support from outside the laboratory for the importance of different Th subsets for resistance to different kinds of parasite, but adds to mounting evidence from natural systems that Th1/Th2 trade-offs observed in laboratory experiments may not readily translate to natural systems 29,32 . Age-specific variation in immunity is widely observed and expected: the immaturity of the immune system in juveniles is often associated with higher parasite burden and less effective responses 37 and this is certainly true of domestic sheep infected with strongyle nematodes 38,39 .…”

“…This demands both the immunological tools for T cell phenotyping, which are lacking for most non-model systems, and protocols for either immediate deployment of assays on live cells in the field or preservation of cells for later analysis 4 . Despite these difficulties, recent studies have begun to explore variation in T cell immunity in wild mammals [28][29][30][31][32] . However, to date, with the exception of some studies in humans 33 , no study in wild mammalian populations has quantified patterns of variation in the full range of Th phenotypes or tested their associations with parasite infection.…”

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

“…However, contrary to our predictions, we found positive rather than negative associations between Th1 and Th2-associated measures. This provides rare support from outside the laboratory for the importance of different Th subsets for resistance to different kinds of parasite, but adds to mounting evidence from natural systems that Th1/Th2 trade-offs observed in reductionist laboratory experiments may not readily translate to complex natural systems (Arriero et al 2017;Young et al 2020).…”

“…Antagonism between Th1 and Th2 responses are well-established in laboratory immunology (Seder & Paul 1994;Mosmann & Sad 1996), and supported by experimental studies of wild buffalo in which Th2-inducing helminth parasites were removed and increased IFN-γ levels (Ezenwa & Jolles 2015). However, data from unmanipulated wild rodent populations provides evidence for synergistic, rather than antagonistic, associations between Th1 and Th2 phenotypes (Arriero et al 2017;Young et al 2020), and indeed work in domestic sheep indicates a complex and temporarily regulated interplay between Th1 and Th2 immune responses is associated with gastro-intestinal parasite resistance (Hassan et al 2011). Variation in resource acquisition, which is common in natural systems, resulting in individual differences in the ability to invest resources in immunity, could readily drive positive associations between different arms of the immune response even if functional trade-offs are present (Noordwijk & Jong 1986;Arriero et al 2017).…”

“…This demands both the immunological tools for T cell phenotyping, which are lacking for most non-model systems, and protocols for either immediate deployment of assays on live cells in the field or careful preservation of cells in the field for later assays (Demas et al 2011). Despite these difficulties, a number of recent studies have begun to explore variation in T cell immunity in wild mammals, by measuring expression of Th master regulator genes in blood samples (Jackson et al 2014;Arriero et al 2017) or by monitoring production of Th1-associated cytokines following ex vivo stimulation of lymphocytes derived from blood samples (Beirne, Delahay & Young 2015;Ezenwa & Jolles 2015;Young et al 2020). However, to date, no study in the wild has quantified patterns of variation in the full range of Th phenotypes illustrated in Figure 1 or tested how they predict levels of natural infection with different parasites.…”