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

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dc.contributor.authorKnott, Michelle L.
dc.contributor.authorMatthaei, Klaus
dc.contributor.authorGiacomin, Paul R
dc.contributor.authorWang, Hui
dc.contributor.authorFoster, Paul S
dc.contributor.authorDent, Lindsay
dc.date.accessioned2015-12-08T22:09:05Z
dc.date.issued2007
dc.date.updated2015-12-08T07:21:55Z
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 ΔdblGATA mice. Resistance to secondary infections was impaired in IL-5-/- and ΔdblGATA 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.identifier.issn0020-7519
dc.identifier.urihttp://hdl.handle.net/1885/28873
dc.publisherElsevier
dc.sourceInternational Journal for Parasitology
dc.subjectKeywords: interleukin 15; transcription factor GATA 1; disease resistance; immune response; nematode; parasitic disease; rodent; skin; vaccine; animal experiment; animal model; animal tissue; article; controlled study; eosinophil; female; immune response; infection Eosinophil; Gut; IL-5; Lungs; Nematode; Nippostrongylus brasiliensis; Primary and secondary infections; Skin
dc.titleImpaired resistance in early secondary Nippostrongylus brasiliensis infections in mice with defective eosinophilopoeisis
dc.typeJournal article
local.bibliographicCitation.issue12
local.bibliographicCitation.lastpage78
local.bibliographicCitation.startpage1367
local.contributor.affiliationKnott, Michelle L., University of Adelaide
local.contributor.affiliationMatthaei, Klaus, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationGiacomin, Paul R, University of Adelaide
local.contributor.affiliationWang, Hui, University of Adelaide
local.contributor.affiliationFoster, Paul S, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationDent, Lindsay, University of Adelaide
local.contributor.authoremailu8200697@anu.edu.au
local.contributor.authoruidMatthaei, Klaus, u8200697
local.contributor.authoruidFoster, Paul S, u8800551
local.description.embargo2037-12-31
local.description.notesImported from ARIES
local.identifier.absfor060502 - Infectious Agents
local.identifier.ariespublicationu4020362xPUB61
local.identifier.citationvolume37
local.identifier.doi10.1016/j.ijpara.2007.04.006
local.identifier.scopusID2-s2.0-34548047670
local.identifier.uidSubmittedByu4020362
local.type.statusPublished Version

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