The opposite roles of PAS-5 and Galectin-1 in immune response during the early infection of Angiostrongylus cantonensis

Abstract

BackgroundAngiostrongylus cantonensis is a human zoonotic nematode parasite. Our previous studies found that PAS-5 and Galectin-1 (Gal-1) proteins of A. cantonensis could be strongly recognized by sera from mice infected with A. cantonensis. In this study, we further evaluated the potential roles of these two proteins in the induction of immune response in mice.MethodsMice were immunized with recombinant PAS-5 or Gal-1 and then challenged with 30 infective A. cantonensis larvae following the last immunization. We then examined the infected mice for changes in serum antibodies and cytokines by ELISA, CD4+ T cells and CD4+CD25+FoxP3+ regulatory T cells (Tregs) by flow cytometry, and tissue damage severity by hematoxylin-eosin (H&E) staining.ResultsCompared with control mice, the PAS-5-immunized mice exhibited increased levels of serum antibodies and cytokines (except for IL-10) at different time points post-infection. PAS-5 immunization promoted significant proliferation of CD4+ T cells, and caused more damage in the brain tissue. Vaccination with Gal-1 inhibited the production of antibodies (except for IgG1) and IFN-γ, but promoted the expression of IL-4 and IL-10. Gal-1 immunization results in significant increases in the levels of CD4+CD25+FoxP3+ Tregs, and mild inflammatory changes.ConclusionsTaken together, our findings show that PAS-5 enhances, but Gal-1 inhibits the immune response in the early stage of A. cantonensis infections.

TNF-α Triggers RIP1/FADD/Caspase-8-Mediated Apoptosis of Astrocytes and RIP3/MLKL-Mediated Necroptosis of Neurons Induced by Angiostrongylus cantonensis Infection

“…As non-permissive hosts of AC (Ji et al 2017 ; Zhou et al 2019 ), mice and human beings could be infected by eating raw or uncooked snails containing third-stage larvae, which causes severe eosinophilic meningitis or encephalitis (Mengying et al 2017 ). Patients infected by AC suffered from a drastic inflammatory response in the host, neurological impairment and neurodegenerative lesions (Yan et al 2018 ; Yoshida et al 1996 ), finally leading to memory and cognitive deterioration as a result of the impaired function and irreversible cell death of brain cells (Mengying et al 2017 ). To date, the treatment for angiostrongyliasis mainly relies on broad-spectrum antiparasitic drugs such as albendazole and treatment of the symptoms.…”

The interaction of host and nematode galectins influences the outcome of gastrointestinal nematode infections

“…The eosinophil-specific chemokinetic activity of H. contortus infective L3 larvae is mediated by nematode galectins in a carbohydrate-dependent manner and may mimic the activity of host galectin 9 (Vasta, 2009). In mice, vaccination against Angiostrongylus cantonensis galectin inhibits the immune response to subsequent infection with A. cantonensis (Yan et al ., 2018). Angiostrongylus cantonensis gal-1 causes apoptosis of macrophages by binding to Annexin A2 and activating the apoptotic signalling pathway (Shi et al ., 2020).…”

Necroptosis and Caspase-2-Mediated Apoptosis of Astrocytes and Neurons, but Not Microglia, of Rat Hippocampus and Parenchyma Caused by Angiostrongylus cantonensis Infection

“…The brains of the rats were serially sectioned (5 µm thick), fixed in 4% paraformaldehyde and paraffin-embedded. The tissues were mounted onto slides and stained with hematoxylin-eosin (H&E) for histopathological observation by using an inverted microscope (Leica, Heidelberg, Germany) as previously described (Yan et al, 2018).…”