Abstract
The animal immune response has hitherto been viewed primarily in the context of resistance only. However, individuals can also employ a tolerance strategy to maintain good health in the face of ongoing infection. To shed light on the genetic and physiological basis of tolerance, we use a natural population of field voles, Microtus agrestis, to search for an association between the expression of the transcription factor Gata3, previously identified as a marker of tolerance in this system, and polymorphism in 84 immune and nonimmune genes. Our results show clear evidence for an association between Gata3 expression and polymorphism in the Fcer1a gene, with the explanatory power of this polymorphism being comparable to that of other nongenetic variables previously identified as important predictors of Gata3 expression. We also uncover the possible mechanism behind this association using an existing protein-protein interaction network for the mouse model rodent, Mus musculus, which we validate using our own expression network for M. agrestis. Our results suggest that the polymorphism in question may be working at the transcriptional level, leading to changes in the expression of the Th2-related genes, Tyrosine-protein kinase BTK and Tyrosine-protein kinase TXK, and hence potentially altering the strength of the Th2 response, of which Gata3 is a mediator. We believe our work has implications for both treatment and control of infectious disease.
Highlights
Tolerance, like resistance, is an active response to infection involving the activation of molecular and physiological mechanisms
We find Gata binding protein 3 (Gata3) expression associated with polymorphism at the Fcer1a gene, and show that the proportion of variation in Gata3 expression explained by this polymorphism is comparable to that explained by other environmental and physiological variables
Gata3 expression is associated with polymorphism in Fcer1a
Summary
Like resistance, is an active response to infection involving the activation of molecular and physiological mechanisms. Rather than preventing or clearing an infection, a tolerance response minimises the disease pathology caused by infection (Caldwell, Schafer, Compton, & Patterson, 1958; Schafer, 1971). This strategy may be favoured where infection is a daily occurrence, or infection is persistent (Restif & Koella, 2004). In these cases, the costs of constantly mounting an immune response in terms of damage to host tissue (immunopathology) may be worse than those of infection itself (Medzhitov, Schneider, & Soares, 2012). Tolerance of infection is attracting considerable interest in the immunological and ecological literature (Medzhitov et al, 2012; Råberg, Graham, & Read, 2009) and provides a new perspective to help understand how the immune response in animals functions following infection, which has hitherto been viewed primarily in the context of resistance only
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