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Frontiers in Immunology 2023Gnathostomiasis is an important zoonosis in tropical areas that is mainly caused by third-stage larvae ( L3).
BACKGROUND
Gnathostomiasis is an important zoonosis in tropical areas that is mainly caused by third-stage larvae ( L3).
OBJECTIVES
This study aimed to prove whether L3 produces extracellular vesicles (EVs) and investigate human gene profiles related to the immune response against the larvae.
METHODS
We created an immune cell model using normal human peripheral blood mononuclear cells (PBMCs) co-cultured with the larvae for 1 and 3 days, respectively. The PBMCs were harvested for transcriptome sequencing analysis. The EV ultrastructure was examined in the larvae and the cultured medium.
RESULTS
Extracellular vesicle-like particles were observed under the larval teguments and in the pellets in the medium. RNA-seq analysis revealed that 2,847 and 3,118 genes were significantly expressed on days 1 and 3 after culture, respectively. The downregulated genes on day 1 after culture were involved in pro-inflammatory cytokines, the complement system and apoptosis, whereas those on day 3 were involved in T cell-dependent B cell activation and wound healing. Significantly upregulated genes related to cell proliferation, activation and development, as well as cytotoxicity, were observed on day 1, and genes regulating T cell maturation, granulocyte function, nuclear factor-κB and toll-like receptor pathways were predominantly observed on day 3 after culture.
CONCLUSION
L3 produces EV-like particles and releases them into the excretory-secretory products. Overall, genotypic findings during our 3-day observation revealed that most significant gene expressions were related to T and B cell signalling, driving T helper 2 cells related to chronic infection, immune evasion of the larvae, and the pathogenesis of gnathostomiasis. Further in-depth studies are necessary to clarify gene functions in the pathogenesis and immune evasion mechanisms of the infective larvae.
Topics: Humans; Animals; Gnathostoma; Larva; Gnathostomiasis; Leukocytes, Mononuclear; Lymphocyte Activation
PubMed: 37600806
DOI: 10.3389/fimmu.2023.1218965 -
Food and Waterborne Parasitology Jun 2024Human gnathostomiasis is a food-borne zoonotic helminthic infection widely reported in Latin America, Asia, and Southeast Asia. Consuming raw, or under-cooked...
Human gnathostomiasis is a food-borne zoonotic helminthic infection widely reported in Latin America, Asia, and Southeast Asia. Consuming raw, or under-cooked fresh-water fish is the leading cause of this helminthic infection, which is clinically characterized by signs of inflammation, itching sensation, or irritation with migratory swelling. Neurological symptoms resulting from neurognathostomiasis vary, and there is scant information due to the rareness of patient brain samples. This study aimed to demonstrate the first evidence of human neurognathostomiasis by the detection of larva in patient's brain during craniotomy, supported by histopathological, immunological and proteomic evidence. Clinical symptoms were obtained from medical history and physical examination with laboratory investigations, including magnetic resonance imaging (MRI), left temporal craniotomy, histopathology of brain tissue, and Western blot analysis, were performed to elucidate the causative pathogens for diagnosis. In addition, the host-parasite interaction of the parasite invading the patient's brain was characterized through proteomics. Histopathology revealed worms with the characteristic cuticular spines of which were detected and identified. These histopathological findings were consistent with a positive Western blot showing a 24-kDa reactive-band for gnathostomiasis. Proteomic analysis revealed the presence of serpin and serine protease in the patient's serum. Moreover, the leucine-rich alpha-2-glycoprotein was indicated as a systemic biomarker of early brain injury related to invasion by Therefore, our study provides the initial evidence of human neurognathostomiasis due to larval invasion along with successful craniotomy and proven larval detection including complete follow-up, and the disease prognosis after surgical treatment.
PubMed: 38774558
DOI: 10.1016/j.fawpar.2024.e00229 -
Food and Waterborne Parasitology Dec 2023is a parasitic nematode that can infect a wide range of animal species, but human populations have become accidental hosts because of their habit of eating raw or... (Review)
Review
is a parasitic nematode that can infect a wide range of animal species, but human populations have become accidental hosts because of their habit of eating raw or undercooked meat from a wide variety of intermediate hosts. While gnathostomiasis is considered an endemic disease, cases of human gnathostomiasis have been increasing over time, most notably in nonendemic areas. There are several complexities to this parasitic disease, and this review provides an update on human gnathostomiasis, including the life cycle, diagnosis, treatment, and treatment strategies used to combat drug resistance. Even now, a definitive diagnosis of gnathostomiasis is still challenging because it is difficult to isolate larvae for parasitological confirmation. Another reason is the varying clinical symptoms recorded in reported cases. Clinical cases can be confirmed by immunodiagnosis. For , the detection of IgG against a specific antigenic band with a molecular weight of 24 kDa from advanced third-stage larvae (aL3), while for other species of including , the 33-kDa antigen protein is being used. This review also discusses cases of recurrence of gnathostomiasis and resistance mechanisms to two effective chemotherapeutics (albendazole and ivermectin) used against gnathostomiasis. This is significant, especially when planning strategies to combat anthelmintic resistance. Lastly, while no new chemotherapeutics against gnathostomiasis have been made available, we describe the management of recurrent gnathostomiasis using albendazole and ivermectin combinations or extensions of drug treatment plans.
PubMed: 37719690
DOI: 10.1016/j.fawpar.2023.e00207