Impaired resistance in early secondary Nippostrongylus brasiliensis infections in mice with defective eosinophilopoeisis

dc.contributor.authorKnott, M.
dc.contributor.authorMatthaei, K.
dc.contributor.authorGiacomin, P.
dc.contributor.authorWang, H.
dc.contributor.authorFoster, P.
dc.contributor.authorDent, L.
dc.date.issued2007
dc.descriptionCopyright © 2007 Australian Society for Parasitology Inc. Published by Elsevier Ltd.
dc.description.abstractEosinophils are an important feature of immune responses to infections with many of the tissue-invasive helminth parasites. The cytokine IL-5 and a high-affinity double GATA-binding site within the GATA-1 promoter are critical for eosinophilopoiesis. In this study, we believe we demonstrate for the first time that defects in eosinophilopoiesis are associated with impaired resistance to Nippostrongylus brasiliensis. Primary and secondary infections were established in wildtype (WT), IL-5(-/-) and DeltadblGATA mice. Resistance to secondary infections was impaired in IL-5(-/-) and DeltadblGATA mice, with significantly more larvae able to reach the lungs 2 days p.i. Pulmonary inflammation was minimal in all strains in the first 2 days of both primary and secondary infections, suggesting that eosinophil-dependent resistance occurred before larvae reached this site. Intestinal worm burdens and/or parasite egg production in primary infections were greater in animals with defective eosinophilopoiesis. While larvae did reach the gut by day 3 of secondary infections of WT and IL-5(-/-) mice, worms were expelled by day 7, even in the complete absence of eosinophils in tissues of the small intestine. This and our previous studies indicate that N. brasiliensis are likely to be exquisitely sensitive to attack by eosinophils soon after entry into the skin. Eosinophils in the gut may make a modest contribution to resistance on first exposure to the parasite, but are not required for expulsion in either primary or secondary infections. In order to mount an effective immune response it may be vital for the host to identify and attack the parasite before it implements immune evasion strategies and migrates to other anatomical sites. These observations may be of particular significance for the development of successful vaccines against hookworms and other nematodes.
dc.description.statementofresponsibilityMichelle L. Knott, Klaus I. Matthaei, Paul R. Giacomin, Hui Wang, Paul S. Foster and Lindsay A. Dent
dc.description.urihttp://www.elsevier.com/wps/find/journaldescription.cws_home/353/description#description
dc.identifier.citationInternational Journal for Parasitology, 2007; 37(12):1367-1378
dc.identifier.doi10.1016/j.ijpara.2007.04.006
dc.identifier.issn0020-7519
dc.identifier.issn1879-0135
dc.identifier.orcidDent, L. [0000-0002-3521-408X]
dc.identifier.urihttp://hdl.handle.net/2440/44517
dc.language.isoen
dc.publisherPergamon-Elsevier Science Ltd
dc.source.urihttps://doi.org/10.1016/j.ijpara.2007.04.006
dc.subjectIL-5
dc.subjectEosinophil
dc.subjectNippostrongylus brasiliensis
dc.subjectNematode
dc.subjectSkin
dc.subjectPrimary and secondary infections
dc.subjectLungs
dc.subjectGut
dc.titleImpaired resistance in early secondary Nippostrongylus brasiliensis infections in mice with defective eosinophilopoeisis
dc.typeJournal article
pubs.publication-statusPublished

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