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Abstract
During the neonatal period, the ability to generate immune effector and memory responses to vaccines or pathogens is often questioned. This study was undertaken to obtain a global view of the natural differences in the expression of immune genes early in life. Our hypothesis was that transcriptome analyses of peripheral blood mononuclear cells (PBMCs) of foals (on day 1 and day 42 after birth) and adult horses would show differential gene expression profiles that characterize natural immune processes. Gene ontology enrichment analysis provided assessment of biological processes affected by age, and a list of 897 genes with ≥2 fold higher (p<0.01) expression in day 42 when compared to day 1 foal samples. Up-regulated genes included B cell and T cell receptor diversity genes; DNA replication enzymes; natural killer cell receptors; granzyme B and perforin; complement receptors; immunomodulatory receptors; cell adhesion molecules; and cytokines/chemokines and their receptors. The list of 1,383 genes that had higher (p<0.01) expression on day 1 when compared to day 42 foal samples was populated by genes with roles in innate immunity such as antimicrobial proteins; pathogen recognition receptors; cytokines/chemokines and their receptors; cell adhesion molecules; co-stimulatory molecules; and T cell receptor delta chain. Within the 742 genes with increased expression between day 42 foal and adult samples, B cell immunity was the main biological process (p = 2.4E-04). Novel data on markedly low (p<0.0001) TLR3 gene expression, and high (p≤0.01) expression of IL27, IL13RA1, IREM-1, SIRL-1, and SIRPα on day 1 compared to day 42 foal samples point out potential mechanisms of increased susceptibility to pathogens in early life. The results portray a progression from innate immune gene expression predominance early in life to adaptive immune gene expression increasing with age with a putative overlay of immune suppressing genes in the neonatal phase. These results provide insight to the unique attributes of the equine neonatal and young immune system, and offer many avenues of future investigation.
Highlights
The naïve neonatal immune system encounters numerous environmental and pathogenic antigens upon leaving the uterus, and faces the task of developing protective immune responses; not responding timely to pathogenic antigens can result in severe infection or death
The transcriptome of peripheral blood mononuclear cells (PBMCs) was sequenced from foals on 1 day of life, from the same foals again on 42 days of life, and from adult horses (n = 4 per age group)
The analyses provided a global overview of immune gene expression at birth, reflective of development in fetal life, and enabled contrasts of lineage-specific immune gene expression during early life and adulthood
Summary
The naïve neonatal immune system encounters numerous environmental and pathogenic antigens upon leaving the uterus, and faces the task of developing protective immune responses; not responding timely to pathogenic antigens can result in severe infection or death. Research findings over the last decade have better defined specific ways in which the neonatal immune system differs from the adult immune system, knowledge gaps still challenge the design and development of long-lasting prophylactic measures for the young age [1,2,3]. The composition of the neonatal immune system differs from the adult in the relative frequency of immune cell populations and expression of selected immune molecules. This difference has been described best in human and mouse neonates and to a lesser extent in other species. An enriched population of CD71+ nucleated red blood cells with immunosuppressive properties has been described in the neonatal humans and mice [9]
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