Infectious Disease and Epigenetics
In our understanding of infectious disease, we tend to imagine something transferred purely through contact; be it a handshake, an open wound, a kiss, or an umbilical cord. But this isn’t always the case. It has become increasingly clear through our study of epigenetics that some infection can embed itself into the readability of our genome, altering the production of our vital proteins. In this way, the effects of infectious disease can be passed down from generation to generation, not just through contact, but through our inherited material.
Epigenetics
Epigenetics is the study of the way genes are regulated and expressed. Histones (around which DNA is wrapped and organized) are the primary proteins involved in DNA regulation. When DNA is wrapped up, it cannot be read, and therefore those genes are not expressed. The process that tightens the DNA around histones is called methylation, where a methyl group is attached to the histone and causes the DNA to condense. Methyl groups can also be added to the DNA strand directly where they act as chemical signals to silence a gene without altering the DNA code itself. In short, methylation helps control which genes are read and the level of gene expression. This secondary sequence of signals is both environmentally controlled and is, in some cases, heritable.
Toxoplasmosis
A new research article published in Parasites & Vectors examines the regulatory effects of Toxoplasma gondii, a parasite that reproduces within cat intestines. (If you own cats, you have likely been warned of the risks associated with cat feces.) Toxoplasmosis, which is caused by consuming undercooked meat or contaminated water, is surprisingly common; it has been estimated that around 30% of the global population is infected. In its chronic form, T. gondii develops cysts in the brain and can increase neuropsychiatric symptoms in its host, such as anxiety, depression, and memory difficulties.
Exploring This Study
The study "The effect of Toxoplasma gondii infection in parental male mice on the transcriptome of their offspring’s brain" by Li et al. focuses on the paternal heritability of toxoplasmosis-impacted traits. Previous studies have made clear the connection between T. gondii infection in male mice and impacted behavior in future generations, but this study focuses primarily on the brain transcriptome (the level of expression of certain key genes).
After infecting the male mice, the researchers waited 14 days before breeding each male with three uninfected females. It is important to note here that due to the reproductive issues that infection caused, only one male mouse was successfully bred. Once the F1 (offspring generation) mice were weaned, all the mice were separated for testing, where they underwent behavioral analysis and brain tissue sampling. The RNA from the brain tissue was then extracted, sequenced, and analyzed.
Li, YN., Sun, H., Ma, J. et al. The effect of Toxoplasma gondii infection in parental male mice on the transcriptome of their offspring’s brain. Parasites Vectors 19, 142 (2026). https://doi.org/10.1186/s13071-026-07302-7
Results
The mice were split into three comparison groups; infected male parent vs male offspring, healthy female parent vs female offspring, and overall parent generation vs all offspring. This allowed for comparisons to be made between the generations as a whole, while accounting for the sex of each individual. Across all three groups, the researchers found 66 differentially expressed genes (DEGs); genes that are expressed to an abnormal level in comparison with a healthy individual. Of these 66 genes, 47 were downregulated (less abundantly expressed than typical) and 19 were upregulated (more abundantly expressed).
These downregulated genes, the study finds, tend to be involved with immune function in the brain. The individuals who inherited these gene expressions are therefore at a higher susceptibility to infection in the brain and are more likely to develop disorders like Alzheimer's. The authors predict that the general downregulation of the transcriptome is likely caused by an increase in RNA m6A methylation (the process by which methyl groups are added directly to RNA strands, thus decreasing their expression). To state it briefly: infection increases RNA methylation in the affected mice's transcriptome, which decreases expression of key genes, which could impair immune function in both parents and offspring.
While there were fewer genes that were upregulated in the affected mice, they still played significant roles. Some of these genes are linked to the immune system, specifically in T-cells and myeloid cells. Others are responsible for neuronal activity in the central nervous system, acting as regulators of memory and cognition. These combined changes in expression may then impact the parent and offspring’s behaviors by altering the communication between the immune and central nervous systems.
While we don’t yet know the full extent to which immune and neurological function would be impaired in affected individuals, the authors highlight the interconnectedness of these genes and the negative long-term effects of their misexpression. More research into these pathways will bring clarity to our understanding of infection in humans, but for now, we are one step closer to understanding how T. gondii affects us and the generations to come.
Cover Image: Nervous Tissue: Spinal Cord Motor Neuron. smear: spinal cord magnification: 100x. Source: Bioscience Image Library by Fayette Reynolds from Unsplash (Public Domain)