Browsing by Keyword "Nippostrongylus brasiliensis"
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Publication Gastrointestinal helminth infection improves insulin sensitivity, decreases systemic inflammation, and alters the composition of gut microbiota in distinct mouse models of Type 2 Diabetes(Frontiers Media, 2020) Khudhair, Zainab; Alhallaf, Rafid; Eichenberger, Ramon M; Whan, Jen; Kupz, Andreas; Field, Matt; Krause, Lutz; Wilson, David T; Daly, Norelle L; Giacomin, Paul; Sotillo, Javier; Loukas, Alex; National Health and Medical Research Council (Australia)Type 2 diabetes (T2D) is a major health problem and is considered one of the top 10 diseases leading to death globally. T2D has been widely associated with systemic and local inflammatory responses and with alterations in the gut microbiota. Microorganisms, including parasitic worms and gut microbes have exquisitely co-evolved with their hosts to establish an immunological interaction that is essential for the formation and maintenance of a balanced immune system, including suppression of excessive inflammation. Herein we show that both prophylactic and therapeutic infection of mice with the parasitic hookworm-like nematode, Nippostrongylus brasiliensis, significantly reduced fasting blood glucose, oral glucose tolerance and body weight gain in two different diet-induced mouse models of T2D. Helminth infection was associated with elevated type 2 immune responses including increased eosinophil numbers in the mesenteric lymph nodes, liver and adipose tissues, as well as increased expression of IL-4 and alternatively activated macrophage marker genes in adipose tissue, liver and gut. N. brasiliensis infection was also associated with significant compositional changes in the gut microbiota at both the phylum and order levels. Our findings show that N. brasiliensis infection drives changes in local and systemic immune cell populations, and that these changes are associated with a reduction in systemic and local inflammation and compositional changes in the gut microbiota which cumulatively might be responsible for the improved insulin sensitivity observed in infected mice. Our findings indicate that carefully controlled therapeutic hookworm infection in humans could be a novel approach for treating metabolic syndrome and thereby preventing 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.Publication Rodent Models for the Study of Soil-Transmitted Helminths: A Proteomics Approach.(Frontiers Media, 2021-04-22) Montaño, Karen J; Cuéllar, Carmen; Sotillo, Javier; Instituto de Salud Carlos III; Unión Europea. Comisión EuropeaSoil-transmitted helminths (STH) affect hundreds of millions worldwide and are some of the most important neglected tropical diseases in terms of morbidity. Due to the difficulty in studying STH human infections, rodent models have become increasingly used, mainly because of their similarities in life cycle. Ascaris suum and Trichuris muris have been proven appropriate and low maintenance models for the study of ascariasis and trichuriasis. In the case of hookworms, despite most of the murine models do not fully reproduce the life cycle of Necator americanus, their proteomic similarity makes them highly suitable for the development of novel vaccine candidates and for the study of hookworm biological features. Furthermore, these models have been helpful in elucidating some basic aspects of our immune system, and are currently being used by numerous researchers to develop novel molecules with immunomodulatory proteins. Herein we review the similarities in the proteomic composition between Nippostrongylus brasiliensis, Heligmosomoides polygyrus bakeri and Trichuris muris and their respective human counterpart with a focus on the vaccine candidates and immunomodulatory proteins being currently studied.