Epigenetics of host-pathogen interactions: the road ahead and the road behind

Abstract

A growing body of evidence points towards epigenetic mechanisms being responsible for a wide range of biological phenomena, from the plasticity of plant growth and development to the nutritional control of caste determination in honeybees and the etiology of human disease (e.g., cancer). With the (partial) elucidation of the molecular basis of epigenetic variation and the heritability of certain of these changes, the field of evolutionary epigenetics is flourishing. Despite this, the role of epigenetics in shaping host-pathogen interactions has received comparatively little attention. Yet there is plenty of evidence supporting the implication of epigenetic mechanisms in the modulation of the biological interaction between hosts and pathogens. The phenotypic plasticity of many key parasite life-history traits appears to be under epigenetic control. Moreover, pathogen-induced effects in host phenotype may have transgenerational consequences, and the bases of these changes and their heritability probably have an epigenetic component. The significance of epigenetic modifications may, however, go beyond providing a mechanistic basis for host and pathogen plasticity. Epigenetic epidemiology has recently emerged as a promising area for future research on infectious diseases. In addition, the incorporation of epigenetic inheritance and epigenetic plasticity mechanisms to evolutionary models and empirical studies of host-pathogen interactions will provide new insights into the evolution and coevolution of these associations. Here, we review the evidence available for the role epigenetics on host-pathogen interactions, and the utility and versatility of the epigenetic technologies available that can be cross-applied to host-pathogen studies. We conclude with recommendations and directions for future research on the burgeoning field of epigenetics as applied to host-pathogen interactions.

Figure 1. Mechanisms of epigenetic plasticity and inheritance.

In single-cell organisms, epimutations induced by environmental stimuli (i.e., host) propagate in daughter cells by mitosis and result in transient or stable epigenetic states. In multicellular, sexually reproducing, organisms the zygote (F1) differentiates into germinal and somatic cells. Epimutations can be originated directly in the germline and propagated by mitosis (“germline induction”) (A), or they can arise and propagate as a consequence of interactions with the soma (“somatic induction”) (B). In the soma, after several rounds of cell divisions, epimutations tend to accumulate during cell and tissue differentiation processes (C). Only those epimutations generated in the germline that escape meiotic resetting during gametogenesis and oogenesis are expected to have transgenerational consequences (i.e., epigenetic inheritance) (F2).

Figure BOX 1

Types of epigenetic modifications. (A) Histones can undergo phosphorylation (Ph), methylation (Me), and acetylation (Ac), among other chemical modifications. These modifications are involved in chromatin remodeling and transcriptional regulation. (B) DNA molecules are methylated by the addition of a methyl group to carbon position 5 on cytosine bases, a reaction catalyzed by DNA methyltransferase enzymes, which maintains repressed gene activity. (C) mRNA is translated into a protein product, but this process can be repressed by binding of microRNAs (miRNA), a class of noncoding RNA (ncRNA). Figure adapted with permission from .

Figure 2. Comparison between the overall number of science citation-indexed publications in the field of epigenetics (black dots) and the number of such publications in the field of host–pathogen interactions (grey dots) over the last 30 years (1980 to 2011).

Search carried out on the Web of Science (Thompson Reuters) on June 2012 using a date-restricted search (1980–2011) and “epigenet*” or “epigenet* and (parasite* or pathogen* or microbe* or bacter* or virus*)” as topic search terms.

Figure 3. Schematic representation of the interrelations between epigenetic variation, phenotypic variation, and host–pathogen interactions.

The infection phenotype, which varies between host and pathogen phenotypes and is environmentally dependent, can induce changes at both the genomic and epigenomic levels. These changes can in turn alter gene expression patterns. Apart from these direct effects of epigenetic variation on host and pathogen phenotypes, epigenetic variation can also have indirect, and transgenerational, phenotypic effects by influencing the probability of mutation, transposition, and/or recombination of the DNA sequence, as well as the predisposition of a gene with a particular epigenetic mark to be selected. See text for further explanation. Red arrows indicate action routes with potential inherited effects (see Figure 1).