DNA methylation of house sparrows differs over time and among tissues and is related to reduced burden of an experimental infection

Introduced species may benefit from highly plastic or general-purpose
responses to infection to overcome the threat of novel pathogens.
Epigenetic mechanisms, particularly DNA methylation, are environmentally
sensitive and flexible regulators of gene expression that may facilitate
responses to infection. The house sparrow (Passer domesticus) has been
successfully introduced across the globe and has substantial variation in
DNA methylation and one form of epigenetic potential (i.e., CpG content of
gene regulatory regions), suggesting that epigenetic plasticity
contributes to introduction success. We investigated whether DNA
methylation in the putative promoter of Toll-like Receptor-04 (TLR4), a
gene important for surveillance of and the instigation of immune responses
to Gram-negative bacteria, was associated with resistance
to pathogenic Salmonella enterica infection. We
quantified DNA methylation across five CpGs in blood at multiple time
points post-infection and in liver, blood, and spleen at euthanasia. DNA
methylation changed rapidly, within 6 hours, after exposure to
bacteria.  Moreover, faster decreases in DNA methylation were
associated with lower terminal Salmonella burden,
suggesting a functional role of induced methylation change in control of
bacterial infection. DNA methylation differed among CpGs in blood samples
across the infection, with the two sites furthest from the transcription
start site showing the strongest declines in DNA methylation. We also
detected DNA methylation differences among tissues at euthanasia: liver
had higher DNA methylation compared to blood and spleen across the
promoter. At the CpG sites, liver DNA methylation was higher at CpGs 1, 2,
and 3 compared to blood and spleen. DNA methylation at CpGs 4 and 5 was
constitutively lower than CpGs 1, 2, and 3 across tissues. This pattern
may suggest that proximity to the transcription start site influences DNA
methylation and hence responsiveness to infection. Our results demonstrate
that DNA methylation in TLR4 is linked to infection outcomes of house
sparrows, which could have contributed to the success of sparrow
introductions.