Infection-induced extracellular vesicles evoke neuronal transcriptional and epigenetic changes

Tedford, Ellen; Badya, Norhidayah Binti; Laing, Conor; Asaoka, Nozomi; Kaneko, Shuji; Filippi, B; McConkey, Glenn A.

doi:10.1038/s41598-023-34074-2

Cited by 5 publications

(5 citation statements)

References 80 publications

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“…Tedford et al 2023). Our results provide additional evidence that the T. gondii -induced reduction of DBH may lead to suppression of defensive behaviors that would normally promote escape from a predator.…”

Section: Discussionmentioning

confidence: 99%

Genetic disruption of dopamine β-hydroxylase dysregulates innate responses to predator odor in mice

Liu

Lustberg

McCann

2023

Preprint

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Rodents infected with the parasite Toxoplasma gondii show reduced aversion to predator odor and diminished neophobia, and infection in humans is associated with increased risk of neuropsychiatric disorders. Norepinephrine (NE) and dopamine (DA) modulate anxiety and predator odor responses, and T. gondii suppresses dopamine β-hydroxylase (Dbh) expression thereby reducing NE and increasing DA, which may contribute to the disruption of innate host behaviors. We examined the consequences of Dbh knockout (Dbh -/-) on responses to predator odor (bobcat urine) and compared them to Dbh-competent littermate controls. Over the first 10 min of predator odor exposure, controls exhibited robust defensive burying behavior, whereas Dbh -/- mice showed high levels of grooming. Defensive burying was potently suppressed in controls by drugs that reduce NE transmission, while excessive grooming in Dbh -/- mice was blocked by DA receptor antagonism. In response to a cotton square scented with a novel neutral odor (lavender), most control mice shredded the material, built a nest, and fell asleep within 90 min. Dbh -/- mice failed to shred the lavender-scented nestlet, but still fell asleep. In contrast, controls sustained high levels of arousal throughout the predator odor test and did not build nests, while Dbh -/- mice were asleep by the 90-min time point, often in shredded bobcat urine-soaked nesting material. Compared with controls exposed to predator odor, Dbh -/- mice demonstrated decreased c-fos induction in the anterior cingulate cortex (ACC), lateral septum (LS), periaqueductal gray (PAG), and bed nucleus of the stria terminalis, but increased c-fos in the LC and medial amygdala. These data indicate that relative ratios of central NE and DA signaling coordinate the type and valence of responses to predator odor, and suggest that Dbh -/- mice may represent a useful monogenetic model of neurobiological changes conferred by T. gondii infection.

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Section: Discussionmentioning

confidence: 99%

Genetic disruption of dopamine β-hydroxylase dysregulates innate responses to predator odor in mice

Liu

Lustberg

McCann

2023

Preprint

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“…Recently, Tedord et al described a novel type of the regulation of neurotransmission mediated by EVs from T. gondii that may contribute to maintaining chronic infection. T. gondii EVs from infected noradrenergic cells were shown to contain a natural mammalian antisense lncRNA that induced gene silencing and DNA hypermethylation in vitro and in the brain [ 89 ].…”

Section: Extracellular Vesicles Secreted By Protozoan Parasitesmentioning

confidence: 99%

“…Similarly, tsRNA in EVs from T. cruzi parasites have been shown to regulate mRNA levels in HeLa cells [ 96 ]. T. gondii EVs carry antisense RNA to downregulate gene expression in murine brain models [ 89 ]. Giardia EVs promote attachment to the host’s cells [ 34 ].…”

Section: Extracellular Vesicles Secreted By Protozoan Parasitesmentioning

confidence: 99%

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Extracellular Vesicles and Their Impact on the Biology of Protozoan Parasites

Sharma,

Lozano-Amado,

Chowdhury

et al. 2023

TropicalMed

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Extracellular vesicles (EVs) are lipid-membrane-bound structures produced naturally by all cells and have a variety of functions. EVs act as vehicles for transporting important molecular signals from one cell to another. Several parasites have been shown to secrete EVs, and their biological functions have been extensively studied. EVs have been shown to facilitate communication with the host cells (such as modulation of the host’s immune system or promoting attachment and invasion into the host cells) or for communication between parasitic cells (e.g., transferring drug-resistance genes or factors modulating stage conversion). It is clear that EVs play an important role in host–parasite interactions. In this review, we summarized the latest research on the EVs secreted by protozoan parasites and their role in host–parasite and parasite–parasite communications.

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“…For example, non-coding RNAs such as miRNAs and long non-coding RNAs have been identified within placental EVs (Luo et al, 2009 ; Morales-Prieto et al, 2020 ). These may induce epigenetic modifications such as DNA methylation (Tedford et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

The ‘communicatome’ of pregnancy: spotlight on cellular and extravesicular chimerism

Graf,

Urbschat,

Arck

2024

EMBO Mol Med

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Communication via biological mediators between mother and fetus are key to reproductive success and offspring’s future health. The repertoire of mediators coding signals between mother and fetus is broad and includes soluble factors, membrane-bound particles and immune as well as non-immune cells. Based on the emergence of technological advancements over the last years, considerable progress has been made toward deciphering the “communicatome” between fetus and mother during pregnancy and even after birth. In this context, pregnancy-associated chimerism has sparked the attention among immunologists, since chimeric cells—although low in number—are maintained in the allogeneic host (mother or fetus) for years after birth. Other non-cellular structures of chimerism, e.g. extracellular vesicles (EVs), are increasingly recognized as modulators of pregnancy outcome and offspring’s health. We here discuss the origin, distribution and function of pregnancy-acquired microchimerism and chimeric EVs in mother and offspring. We also highlight the pioneering concept of maternal microchimeric cell-derived EVs in offspring. Such insights expand the understanding of pregnancy-associated health or disease risks in mother and offspring.

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Infection-induced extracellular vesicles evoke neuronal transcriptional and epigenetic changes

Cited by 5 publications

References 80 publications

Genetic disruption of dopamine β-hydroxylase dysregulates innate responses to predator odor in mice

Genetic disruption of dopamine β-hydroxylase dysregulates innate responses to predator odor in mice

Extracellular Vesicles and Their Impact on the Biology of Protozoan Parasites

The ‘communicatome’ of pregnancy: spotlight on cellular and extravesicular chimerism

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