McKernan, D. | Search bioRxiv

bioRxiv2025

The anti-inflammatory potential of helminth-derived peptides/polypeptides: A systematic review in cellular models of inflammation

Helminths are parasitic worms that secrete a plethora of immune regulatory molecules which allow them to dampen inflammatory responses by their hosts immune system to ensure their survival within the host. Their ability to have a compatible existence with their host has led to research into the potential therapeutic effects of helminth-derived molecules for suppression of overactive immune and inflammatory responses in a wide variety of diseases. This systematic review aims to synthesize the published data on helminth-derived peptides/polypeptides (HDPs) with a focus on determining the extent to which they modulate the inflammatory response in in vitro cellular models of inflammation. In accordance with PRISMA 2020 guidelines, a predefined systematic search of the PubMed, Web of Science and Medline databases identified relevant studies published up to August 2025, and 79 articles were included after screening. We found that most published studies used LPS or Concanavalin A stimulated macrophages, peripheral blood mononuclear cells or dendritic cells as the cellular model of inflammation. Twenty helminth species from which >60 isolated HDPs were derived were tested in these models, with the nematodes, Haemonchus contortus and Acanthocheilonema viteae, and the trematode, Fasciola hepatica, the most explored species. A common property of these molecules was to ability to significantly reduce the expression or production of pro-inflammatory cytokines such as IL-12, IL-1{beta}, IL-6 and TNF, and significantly increase the expression or production of anti-inflammatory cytokines such as IL-10, TGF{beta} and IL-4. The effects on other cytokines, including IFN{gamma} which is known to have both pro- and anti-inflammatory effects, were less consistent, with HDPs either decreasing or increasing the levels of this cytokine. This systematic review synthesizes the existing literature in this field and shows that the HDPs secreted by several helminth species have consistently demonstrated effects though modification of cytokine levels and, as such, have therapeutic potential in conditions in which overactive immune and inflammatory responses play a pathogenic role.

immunology↗

bioRxiv2023

Social isolation-induced transcriptomic changes in mouse hippocampus impact the synapse and show convergence with human genetic risk for neurodevelopmental phenotypes

Early life stress (ELS) can impact brain development and is a risk factor for neurodevelopmental disorders such as schizophrenia. Post-weaning social isolation (SI) is used to model ELS in animals, using isolation stress to disrupt a normal developmental trajectory. We aimed to investigate how SI affects the expression of genes in mouse hippocampus and to investigate how these changes related to the genetic basis of neurodevelopmental phenotypes. BL/6J mice were exposed to post-weaning SI (PD21-25) or treated as group-housed controls (n = 7-8 per group). RNA sequencing was performed on tissue samples from the hippocampus of adult male and female mice. Four hundred and 1,215 differentially-expressed genes (DEGs) at a false discovery rate of < 0.05 were detected between SI and control samples for males and females respectively. DEGS for both males and females were significantly overrepresented in gene ontologies related to synaptic structure and function, especially the post-synapse. DEGs were enriched for common variant (SNP) heritability in humans that contributes to risk of neuropsychiatric disorders (schizophrenia, bipolar disorder) and to cognitive function. DEGs were also enriched for genes harbouring rare de novo variants that contribute to autism spectrum disorder and other developmental disorders. Finally, cell type analysis revealed populations of hippocampal astrocytes that were enriched for DEGs, indicating effects in these cell types as well as neurons. Overall, these data suggest a convergence between genes dysregulated by the SI stressor in the mouse and genes associated with neurodevelopmental disorders and cognitive phenotypes in humans. Author SummaryEarly life stress increases risk of developing neuropsychiatric and neurodevelopmental disorders. Early life stress can be modelled in animals using social isolation (SI) where animals are separated from others after they have stopped weaning and are housed individually rather than in groups. Here, we investigated the effect of SI on gene expression in the hippocampus, a brain region that regulates stress response and emotion, and how this relates to the known genetic aetiology of neuropsychiatric disorders and traits such as cognitive function. We found that genes altered by SI play a role in how synapses form and function - these are the connection points between nerve cells in the brain. We also found these altered genes are also the genes where common changes in the DNA code can increase risk for schizophrenia, bipolar disorder and influence cognitive ability, and where rare changes in the DNA code increase risk for autism spectrum disorder and developmental disorder. Finally, these genes altered by SI are also highly expressed in astrocytes, cells that help nerve cells to function in the hippocampus. Overall, these data suggest a convergence between genes affected by SI, the environmental stressor, and the genes associated with neurodevelopmental disorders and cognition.

genomics↗