Strongyloides stercoralis:Eosinophil-Dependent Immune-Mediated Killing of Third Stage Larvae in BALB/cByJ Mice

Rotman, Harris L.; Yutanawiboonchai, Wiboonchai; Brigandi, Richard A.; Leon, Ofra; Gleich, Gerald J.; Nolan, Thomas J.; Schad, Gerhard A.; Abraham, David

doi:10.1006/expr.1996.0034

Cited by 102 publications

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“…These findings confirm previous reports in which elimination of IL-5 by mAb treatment (TRFK-5) was shown to abrogate S. stercoralis larval killing in immunized BALB/cByJ mice (18). In contrast, many other groups have found no role for IL-5 in protection from other parasites, however measurable levels of eosinophils could still be found in the peripheral blood, cutaneous tissues, cerebrospinal fluid, liver, and lungs of TRFK-5-treated mice (12,35,(37)(38)(39)(40)(41)(42)(43).…”

Section: Discussionsupporting

confidence: 92%

“…A similar result was obtained using a different IL-5 transgenic mouse strain where it was reported that naive mice infected with infective stage larvae of Nippostrongylus brasiliensis showed eosinophil recruitment within 6 h postinfection and a significant decrease in worm burden within 72 h postinfection (36). A direct role for eosinophil killing of larval S. stercoralis has been demonstrated in vitro, where it was shown that the human eosinophil granule proteins major basic protein and eosinophil cationic protein were toxic to S. stercoralis larvae, whereas EPO and eosinophil-derived neurotoxin were not (18). Killing with major basic protein and eosinophil cationic protein only occurred after the larvae had undergone development under mammalian ambient conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, a role for IL-5 has been established in protective immunity against the nematodes Onchocerca volvulus (15), Onchocerca lienalis (16), Angiostrongylus cantonensis (17), Strongyloides stercoralis (18), and Strongyloides ratti (19). These nematodes showed an increased parasite burden, delayed expulsion, or impaired clearance of infection when the levels of IL-5 were reduced by treatment with the mAb TRFK-5.…”

mentioning

confidence: 99%

“…It was shown that TRFK-5 ablated immunity if the challenge larvae were localized within diffusion chambers, but not if the larvae were injected into the tissues of the mouse and allowed to migrate systemically (18). One interpretation of these results is that the anti-IL-5 treatment functioned in elimination of immunity against parasites contained within diffusion chambers because of an artifact caused by the diffusion chamber preventing parasite migration away from effector cells.…”

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confidence: 99%

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Role of IL-5 in Innate and Adaptive Immunity to LarvalStrongyloides stercoralisin Mice

Herbert

Lee

et al. 2000

The Journal of Immunology

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Protective immunity to Strongyloides stercoralis infective larvae in mice has been shown to be dependent on IL-5 based on mAb depletion studies. The goal of this study was to determine the functional role of IL-5 during the innate and adaptive immune response to larval S. stercoralis in mice. In these studies, three strains of mice were used: wild-type C57BL/6J (WT), IL-5 knockout (KO), and IL-5 transgenic (TG). Innate responses to the larvae indicated that there was enhanced survival in the KO animals and decreased survival in the TG animals compared with WT. Furthermore, killing of larvae in TG mice was associated with eosinophil infiltration and degranulation. In studying the adaptive immune response, it was observed that immunization of KO mice did not lead to the development of protective immunity. Experiments were then performed to determine whether KO mice reconstituted with Abs or cells could then develop protective immunity. KO mice displayed protective immunity via a granulocyte-dependent mechanism following injection of purified IgM from immune wild-type animals. Immunity in KO mice could also be reconstituted by the injection of eosinophils at the time of immunization. These eosinophils did not participate in actively killing the challenge infection, but rather were responsible for the induction of a protective Ab response. We conclude that IL-5 is required in the protective immune response for the production of eosinophils, and that eosinophils were involved in larval killing during innate immunity and in the induction of protective Abs in the adaptive immune response.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Role of IL-5 in Innate and Adaptive Immunity to LarvalStrongyloides stercoralisin Mice

Herbert

Lee

et al. 2000

The Journal of Immunology

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113

110

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“…Similar in vitro findings were also reported in the study with Nippostrongylus brasiliensis in mice [13]. Moreover, by using Strongyloides stercoralis L3 in diffusion chambers implanted in immunised mice, Rotman et al [11] have demonstrated that the majority of the cells recruited towards the larvae are eosinophils and maximal cell number coincides with parasite killing. In this study, it was suggested that direct contact between the cells and the L3 is required for larval killing.…”

Section: Discussionsupporting

confidence: 82%

In vitro pre-exposure ofHaemonchus contortusL3 to blood eosinophils reduces their establishment potential in sheep

et al. 2007

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-Different authors have reported that eosinophils are capable of immobilising infective larvae of different species of nematodes in vitro. However, classifying larvae as mobile or immobile is so subjective that it does not always mean all apparently immobile larvae are dead or those that are mobile are capable of surviving further immune responses if administered to their natural hosts. The objective of this experimental study was therefore to substantiate the role of eosinophils in the killing of Haemonchus contortus infective larvae by comparing the infectivity in sheep of larvae that had been incubated with eosinophil-enriched cell suspensions with control larvae. Since it was not possible to isolate pure eosinophils from sheep blood, we were compelled to evaluate the effects of other blood cells contaminating our eosinophil-enriched suspensions. Although eosinophils and neutrophils were the only cells found adherent to H. contortus infective larvae in vitro, induced eosinophils in the presence of immune serum were primarily responsible for the drastic reduction in larval motility compared to the minor effects of neutrophils and mononuclear cells. Corresponding reductions in faecal egg count and worm numbers were observed when the incubated larvae were transferred intra-abomasally to sheep. Interestingly, the proportion of larvae that failed to establish was much higher following incubation with induced eosinophils compared with other cells or with immune serum alone. Although this study did not address the in vivo role of eosinophils in sheep, the results strongly indicate that sheep blood eosinophils have a larval killing potential in vitro, and a larval mobility test alone may not fully explain the level of damage inflicted on the larvae.Haemonchus contortus / eosinophils / in vitro / intra-abomasal / sheep

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Eotaxin‐1‐regulated eosinophils have a critical role in innate immunity against experimental Brugia malayi infection

2004

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Using two models of filarial infection in which Brugia malayi microfilariae (Mf) are contained in distinct anatomical compartments, in blood or tissue sites, we have demonstrated a critical role for eotaxin-1 in parasite clearance. In the first model, implantation of adult B. malayi into the peritoneal cavity of eotaxin-1 -/-mice resulted in increased Mf survival associated with a dramatic reduction in peritoneal cavity eosinophilic infiltration. In the second model Mf were injected intravenously into eotaxin-1 -/-mice; Mf clearance from the blood was more rapid than in wild-type mice and was associated with a pronounced blood eosinophilia, resulting from the inability of eosinophils to migrate to tissue sites in the absence of eotaxin-1. (Eotaxin-1 + IL-5) -/-mice had extended Mf survival in the blood and significantly reduced blood eosinophil levels. Interestingly, rapid clearance of a secondary Mf infection following immunization was unaltered in either eotaxin-1 -/-mice or (eotaxin-1 + IL-5) -/-mice. Eosinophil peroxidase levels were high during primary, but not secondary infection, suggesting that eosinophil degranulation is important during primary Mf clearance. Thus, our data show that the presence of eosinophils is critical for innate clearance of B. malayi Mf infection, whereas rapid clearance of secondary infections is independent of both eotaxin-1 and IL-5.

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Strongyloides stercoralis:Eosinophil-Dependent Immune-Mediated Killing of Third Stage Larvae in BALB/cByJ Mice

Cited by 102 publications

References 0 publications

Role of IL-5 in Innate and Adaptive Immunity to LarvalStrongyloides stercoralisin Mice

Role of IL-5 in Innate and Adaptive Immunity to LarvalStrongyloides stercoralisin Mice

In vitro pre-exposure ofHaemonchus contortusL3 to blood eosinophils reduces their establishment potential in sheep

Eotaxin‐1‐regulated eosinophils have a critical role in innate immunity against experimental Brugia malayi infection

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