Epigenetic Signature of Exposure to Maternal Trypanosoma Cruzi Infection in Cord Blood Cells from Uninfected Newborns

Abstract

Aims: To assess the epigenetic effects of in utero exposure to maternal Trypanosoma cruzi infection. Methods: We performed an epigenome-wide association study to compare the DNA methylation patterns of umbilical cord blood cells from uninfected babies from chagasic and uninfected mothers. DNA methylation was measured using Infinium EPIC arrays. Results: We identified a differential DNA methylation signature of fetal exposure to maternal T. cruzi infection, in the absence of parasite transmission, with 12 differentially methylated sites in B cells and CD4⁺ T cells, including eight protein-coding genes. Conclusion: These genes participate in hematopoietic cell differentiation and the immune response and may be involved in immune disorders. They also have been associated with several developmental disorders and syndromes.

Plain language summary

Maternal infection with Trypanosoma cruzi, the parasite that causes Chagas disease, may influence fetal development, even in the absence of parasite transmission. Thus we investigated how exposure to maternal infection might lead to changes in gene expression in the infant, by examining changes in DNA methylation in the umbilical cord blood. We found that exposure to maternal infection alters DNA methylation of at least 12 sites, including eight genes. Expression of these genes may be altered, which may affect blood cell function, the immune response and newborn development later in life. Further studies should monitor newborns from infected mothers to better assess their health and possible longer term effects.

Keywords::

• Chagas disease
• DNA methylation
• parasite
• pregnancy
• Trypanosoma cruzi

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2022-0153

Author contributions

Conception: P Buekens, C Herrera and E Dumonteil. Design of the work: P Buekens, C Herrera, C Truyens and E Dumonteil. Data acquisition and analysis: H Desale, C Herrera, J Alger, M Cafferata, E Harville, C Herrera, C Truyens and E Dumonteil. Interpretation of data: all authors. Drafting the manuscript: H Desale. Manuscript revisions: all authors. Approval of the submitted version: all authors.

Financial & competing interests disclosure

The study was funded in part by NIH/NIAID (R01AI083563). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

Array data have been deposited into the NCBI GEO database under accession number GSE198495.

Additional information

Funding

The study was funded in part by NIH/NIAID (R01AI083563). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.