Guangxu Ma

Parasitic nematodes encode a limited repertoire of insulin/insulin-like peptides (INS/ILPs) which are expressed primarily in free-living stages, suggesting that host insulin may serve as a critical agonist during parasitism. In this study, we demonstrate that mammalian parasitic nematodes exploit host insulin via their conserved insulin/insulin-like growth factor receptor (IGFR/DAF-2) to drive infection and reproduction in vitro and in vivo. Specifically, host insulin supplementation promotes the biosynthesis of the steroid hormone Δ7-dafachronic acid, the activation of nuclear receptor DAF-12, the infective-to-parasitic transition, and the larval motility and growth in Haemonchus contortus, a model gastrointestinal blood-feeding nematode. Structural analyses suggest that H. contortus IGFR/DAF-2 can bind host (Ovis aries) insulin with predicted affinity comparable to endogenous peptides while engaging a distinct receptor-binding site. Notably, RNAi-mediated silencing of daf-2 impairs larval development, reduces worm burden, and compromises egg production in host animals. Furthermore, we uncover a novel role for insulin signalling in regulating the nematode female-to-male ratio, possibly through sex determination or selective female mortality, specifically affecting female development and reproduction. These findings establish the ligand-receptor co-option of host insulin signalling as an evolutionary adaptation to parasitism and identify IGFR/DAF-2 as a potential target for controlling nematode infection, transmission, and population dynamics.

Toxocara canis is a globally distributed parasite that infects dogs and other canids, shedding eggs into the environment. Humans become accidental hosts by ingesting infective eggs, leading to syndromes such as visceral, ocular and neurotoxocariasis – the latter being poorly understood. Neurotoxocariasis has been proposed to be associated with epilepsy, cognitive impairment and schizophrenia, but its pathomechanism remains unclear. Here, we combine spatial transcriptomics, single-nucleus RNA sequencing, lipidomics and behavioural assays in a mouse model to characterise the host–parasite interface in the brain. T. canis larvae induce region-specific neural injury, vascular remodelling, and spatially confined immune responses, accompanied by parasite transcriptional programmes dominated by immunomodulatory factors and developmental regulators. Infected mice exhibit impairments in motor learning and memory, coinciding with transcriptional changes in neurons and glia. These findings provide mechanistic insight into neurotoxocariasis and demonstrate the utility of the mouse model as a platform to investigate helminth-induced neurological disorders.

Hematophagy is essential for the survival and development of blood-feeding nematodes, including Haemonchus contortus (the barber’s pole worm) – a gastrointestinal nematode model for the study of anthelmintic resistance and drug discovery. Upon host ingestion, the infective larvae of this nematode transit to parasitic stage, then consume blood, contributing to the pathology of haemonchosis, a disease responsible for substantial economic losses. However, this process cannot be replicated in vitro without blood supplements. Therefore, despite genomic insights into developmental biology and anthelmintic resistance mechanisms, hematophagy remains poorly understood in this and other blood-feeding species. Here, we present a transcriptome dataset from the in vitro-cultured parasitic larvae of H. contortus exposed to 100 µM hemin chloride, 10% serum, and 10% defibrinated blood of host animals. A proteomic dataset for the in vitro-cultured larvae exposed to 10% serum is also available. These resources enable exploration of blood-component-specific transcriptomic reprogramming, hub gene-driven translational/metabolic modules, and molecular adaptations. This dataset also enables identification of genes critical for blood-feeding adaptation and parasitism, advancing therapeutic targets for intervention.

Over the past decade, small RNA technologies have been proposed for improved control of parasitic worms. Although achievements have been made in the identification of target candidates and in the improvement of reverse genetic tools, few of those have been tested in domestic animals. In this work, crucial genes (i.e., daf-9/cyp-22a1, bli-5 and HCON_00083600) involved in the developmental transition (i.e., activation, moulting and haem utilisation) from the infective L3 stage to the parasitic L4 stage of Haemonchus contortus (the barber’s pole worm commonly found in small ruminants) in vitro were identified and verified using RNA interference (RNAi) technologies during the adaptation to parasitism of this parasite in vivo. Silencing each of the daf-9/cyp-22a1, bli-5 and HCON_00083600 genes in the infective larvae of H. contortus resulted in compromised larval development and viability in vitro, and silencing of either the daf-9/cyp-22a1, bli-5 or HCON_00083600 gene led to a marked reduction in the faecal egg count and worm burden in sheep. In conclusion, the results demonstrate that genes involved in larval activation, moulting and haem utilisation of H. contortus are target candidates, and the application of RNAi technologies for better control of these and related parasitic nematodes is promising, preferably with an improved RNAi tool for efficient and long-lasting effects in host animals.

Toxocara canis is a globally distributed parasite that infects dogs and other canids, shedding eggs into the environment. Humans become accidental hosts by ingesting these eggs, leading to syndromes such as visceral, ocular and neurotoxocariasis – the latter being poorly understood. Neurotoxocariasis has been associated with epilepsy, cognitive impairment and schizophrenia, but its pathomechanism remains unclear. Here, we combine spatial transcriptomics, single-nucleus RNA sequencing and behavioural assays in a mouse model to characterise the host–parasite interface in the brain. T. canis larvae caused region-specific brain damage, vascular remodelling and confined immune responses. Parasite gene expression was dominated by immunomodulatory excretory/secretory proteins. Infected mice exhibited impairments in motor learning and memory, coinciding with transcriptional changes in neurons and glia. These findings provide mechanistic insight into neurotoxocariasis and demonstrate the utility of the mouse model as a platform to investigate helminth-induced neurological disorders.

Background: Human toxocariasis, caused by the zoonotic parasites Toxocara canis (dog roundworm) and T. cati (cat roundworm), affects approximately 19% of the global population, ranking it among the most prevalent neglected infection of poverty. However, public awareness about this zoonotic disease has not yet been achieved in China. In this study, we conducted an epidemiological survey to assess the prevalence and risk factors of Toxocara infection in dogs and cats, as well as toxocariasis or Toxocara exposure in humans in Zhejiang. Methods: An epidemiological survey was conducted between January 2023 and April 2024 to ascertain the prevalence of Toxocara infection in Zhejiang, where has been set to be a model for common prosperity in China. Fecal samples from dogs (n = 1156) and cats (n = 818) were examined for Toxocara eggs using the saturated saline floatation method and molecular tools, while human serum samples (n = 347) were tested for antibodies against Toxocara species by an enzyme-linked immunosorbent assay. Risk factors for Toxocara infection in dogs, cats and humans were analyzed using logistic regression models. Results: The overall prevalence of Toxocara infection was 5.36% in dogs, 2.08% in cats, and 12.10% in humans in Zhejiang, China. Age (≤ 6 months, OR = 6.22, P = 0.026), season (autumn, OR = 13.93, P = 0.017 and spring, OR = 11.07, P = 0.027) and deworming frequency (< 4 times/year, OR = 0.18, P < 0.001) were identified as major risk factors for T. canis infection in dogs, whereas residing in an animal shelter (OR = 13.14, P = 0.020) was a risk factor for T. cati infection in cats. Occupation exposure (OR = 4.53, P = 0.009) was the most significant risk factor for Toxocara infection in humans. Conclusions: Due to the good economic status and social welfare, the prevalence of Toxocara infection in dogs, cats and humans is relatively low in Zhejiang, China. However, an “One Health” paradigm about human toxocariasis intervention is lacking and the risk factors (particularly pet deworming and occupational exposure) for Toxocara infection and transmission warrant improved public awareness. Graphical

弓形虫(Toxoplasma gondii)是一种专性胞内寄生的顶复门原

Background: The mitochondrion is proposed as an ideal target organelle for the control of apicomplexan parasites, whose integrity depends on well-controlled protein import, folding, and turnover. The ubiquitin-like domain-containing C-terminal domain phosphatase 1 (UBLCP1) was found to be associated with the mitochondrial integrity in Toxoplasma gondii. However, little is known about the roles and mechanisms of UBLCP1 in this apicomplexan parasite. Methods: The subcellular localization of UBLCP1 in the tachyzoites of T. gondii was determined by an indirect immunofluorescence assay. The roles of UBLCP1 in the growth, cell cycle, and division of T. gondii were assessed by knocking out this molecule in the tachyzoites. Comparative phosphoproteomics between the UBLCP1-deficient and wild-type tachyzoites were performed to understand the roles of UBLCP1 in T. gondii. The virulence of UBLCP1-deficient tachyzoites of T. gondii was tested in mice. Results: UBLCP1 is expressed in the nucleus and cytoplasm of T. gondii tachyzoites. Tachyzoites lacking UBLCP1 exhibit collapsed mitochondrion, decreased mitochondrial membrane potential, and compromised growth and proliferation in vitro. Proteins involved in protein turnover and intracellular trafficking have been found differentially phosphorylated in the UBLCP1-deficient tachyzoites compared with the control. Deletion of UBLCP1 also shows that this phosphatase is essential for the propagation and virulence of T. gondii tachyzoites. Mice immunized with UBLCP1-deficient T. gondii tachyzoites survived challenges with the virulent PRU or VEG strain. Conclusions: UBLCP1 is required for the mitochondrial integrity and essential in the lytic cycle (e.g., host cell invasion and parasite replication) in vitro and the pathogenicity of this parasite in vivo. UBLCP1 is a candidate target for a vaccine or a drug for toxoplasmosis in animals. Graphical