Browsing by MeSH term "Nippostrongylus"
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Publication Administration of Hookworm Excretory/Secretory Proteins Improves Glucose Tolerance in a Mouse Model of Type 2 Diabetes(Multidisciplinary Digital Publishing Institute (MDPI), 2022-04-26) Khudhair, Zainab; Alhallaf, Rafid; Eichenberger, Ramon M; Field, Matt; Krause, Lutz; Sotillo, Javier; Loukas, Alex; Eichenberger, Ramon M.; National Health and Medical Research Council (Australia); Australian Research Council; Australian Institute of Tropical Health and Medicine; James Cook University (Australia)Diabetes is recognised as the world's fastest growing chronic condition globally. Helminth infections have been shown to be associated with a lower prevalence of type 2 diabetes (T2D), in part due to their ability to induce a type 2 immune response. Therefore, to understand the molecular mechanisms that underlie the development of T2D-induced insulin resistance, we treated mice fed on normal or diabetes-promoting diets with excretory/secretory products (ES) from the gastrointestinal helminth Nippostrongylus brasiliensis. We demonstrated that treatment with crude ES products from adult worms (AES) or infective third-stage larvae (L3ES) from N. brasiliensis improved glucose tolerance and attenuated body weight gain in mice fed on a high glycaemic index diet. N. brasiliensis ES administration to mice was associated with a type 2 immune response measured by increased eosinophils and IL-5 in peripheral tissues but not IL-4, and with a decrease in the level of IL-6 in adipose tissue and corresponding increase in IL-6 levels in the liver. Moreover, treatment with AES or L3ES was associated with significant changes in the community composition of the gut microbiota at the phylum and order levels. These data highlight a role for N. brasiliensis ES in modulating the immune response associated with T2D, and suggest that N. brasiliensis ES contain molecules with therapeutic potential for treating metabolic syndrome and T2D.Publication Hookworms Evade Host Immunity by Secreting a Deoxyribonuclease to Degrade Neutrophil Extracellular Traps.(Cell Press, 2020) Bouchery, Tiffany; Moyat, Mati; Sotillo, Javier; Silverstein, Solomon; Volpe, Beatrice; Coakley, Gillian; Tsourouktsoglou, Theodora-Dorita; Becker, Luke; Shah, Kathleen; Kulagin, Manuel; Guiet, Romain; Camberis, Mali; Schmidt, Alfonso; Seitz, Arne; Giacomin, Paul; Le Gros, Graham; Papayannopoulos, Venizelos; Loukas, Alex; Harris, Nicola L; Swiss National Science Foundation; National Health and Medical Research Council (Australia)Hookworms cause a major neglected tropical disease, occurring after larvae penetrate the host skin. Neutrophils are phagocytes that kill large pathogens by releasing neutrophil extracellular traps (NETs), but whether they target hookworms during skin infection is unknown. Using a murine hookworm, Nippostrongylus brasiliensis, we observed neutrophils being rapidly recruited and deploying NETs around skin-penetrating larvae. Neutrophils depletion or NET inhibition altered larvae behavior and enhanced the number of adult worms following murine infection. Nevertheless, larvae were able to mitigate the effect of NETs by secreting a deoxyribonuclease (Nb-DNase II) to degrade the DNA backbone. Critically, neutrophils were able to kill larvae in vitro, which was enhanced by neutralizing Nb-DNase II. Homologs of Nb-DNase II are present in other nematodes, including the human hookworm, Necator americanus, which also evaded NETs in vitro. These findings highlight the importance of neutrophils in hookworm infection and a potential conserved mechanism of immune evasion.