A hookworm allergen which strongly resembles calreticulin

Pritchard, David; Brown, Alan; Kasper, Grit; McElroy, Paul J.; Loukas, Alex; Hewitt, Colin R. A.; Berry, Colin; Fullkrug, Ralf; Beck, Ewald

doi:10.1046/j.1365-3024.1999.00238.x

Cited by 64 publications

(50 citation statements)

References 38 publications

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“…Other allergens capable of direct immunomodulation have also been described; for instance, the Der p 1 allergen of the house dust mite Dermatophagoides pteronyssinus proteolytically cleaves CD25 on T cells, which promotes IL-4 expression at the expense of IFN-␥, resulting in enhanced IgE production (52). A calreticulin-like molecule secreted by Nector americanus is also an allergen and target of IgE responses in infected humans (49). Its activity appears to be mediated by inhibition of the biological function of human C1q and binding to the cytoplasmic signaling domains of a number of integrins (28).…”

Section: Discussionmentioning

confidence: 99%

Modulation of a Heterologous Immune Response by the Products ofAscaris suum

et al. 2002

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Helminth infections are among the most potent stimulators of Th2-type immune responses and have been widely demonstrated to modify responsiveness to both nonparasite antigens and other infectious agents in a nonspecific manner in infected animals. We investigated the immunomodulatory properties of pseudocoelomic body fluid from adult Ascaris suum gastrointestinal helminths (ABF) and its defined allergen (ABA-1) by examining their effects on the immune response to a heterologous antigen, ovalbumin. Our results indicate that ABF has potent immunomodulatory activity and that the effects observed are consistent with skewing towards a Th2-type response rather than induction of anergy. Our findings show that the immunomodulatory activities of ABF are associated with components other than the major constituent and putative allergen, ABA-1. Furthermore, the allergic responses to ABA-1 are not a result of an intrinsic allergenicity of the protein but are more a reflection of the wider induction of a Th2 response by the infection. Importantly, the induction of interleukin-10 by ABF also suggests that T regulatory cells may play a role in immunomodulation of immune responses by parasitic helminths.

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Section: Discussionmentioning

confidence: 99%

Modulation of a Heterologous Immune Response by the Products ofAscaris suum

et al. 2002

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“…), and L3NIEAG.01, represented by three clusters, is a putative member of the Ancylostoma secreted protein (ASP) family (Hawdon et al 1996). Among transcripts abundant in both stages are SS01569.cl with homology to genes encoding calreticulin-related antigens in Necator americanus (Pritchard et al 1999) and Onchocerca volvulus (Rokeach et al 1994), and SS01566.cl with weak homology to the immunodominant hypodermal C. elegans homolog present but with a lower probability match than the best GenBank descriptor.…”

Section: Abundant Transcripts Expressed In L1 Versus L3imentioning

confidence: 99%

Comparative Genomics of Gene Expression in the Parasitic and Free-Living Nematodes Strongyloides stercoralis and Caenorhabditis elegans

Mitreva¹,

McCarter²,

Martin³

et al. 2004

Genome Res.

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Although developmental timing of gene expression is used to infer potential gene function, studies have yet to correlate this information between species. We analyzed 10,921 ESTs in 3311 clusters from first-and infective third-stage larva (L1, L3i) of the parasitic nematode Strongyloides stercoralis and compared the results to Caenorhabditis elegans, a species that has an L3i-like dauer stage. In the comparison of S. stercoralis clusters with stage-specific expression to C. elegans homologs expressed in either dauer or nondauer stages, matches between S. stercoralis L1 and C. elegans nondauer-expressed genes dominated, suggesting conservation in the repertoire of genes expressed during growth in nutrient-rich conditions. For example, S. stercoralis collagen transcripts were abundant in L1 but not L3i, a pattern consistent with C. elegans collagens. Although a greater proportion of S. stercoralis L3i than L1 genes have homologs among the C. elegans dauer-specific transcripts, we did not uncover evidence of a robust conserved L3i/dauer 'expression signature.' Strikingly, in comparisons of S. stercoralis clusters to C. elegans homologs with RNAi knockouts, those with significant L1-specific expression were more than twice as likely as L3i-specific clusters to match genes with phenotypes. We also provide functional classifications of S. stercoralis clusters.

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“…Probably found in the secretions of N. americanus, calreticulin was recently shown to be the major allergen recognized by IgE from patients infected with the parasite (108). Its role as an extracellular secreted product of nematodes remains speculative, but some intriguing immunomodulatory properties can be extrapolated from studies with mammalian calreticulin.…”

Section: Calreticulinmentioning

confidence: 99%

Immune Responses in Hookworm Infections

2001

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Hookworms infect perhaps one-fifth of the entire human population, yet little is known about their interaction with our immune system. The two major species are Necator americanus, which is adapted to tropical conditions, and Ancylostoma duodenale, which predominates in more temperate zones. While having many common features, they also differ in several key aspects of their biology. Host immune responses are triggered by larval invasion of the skin, larval migration through the circulation and lungs, and worm establishment in the intestine, where adult worms feed on blood and mucosa while injecting various molecules that facilitate feeding and modulate host protective responses. Despite repeated exposure, protective immunity does not seem to develop in humans, so that infections occur in all age groups (depending on exposure patterns) and tend to be prolonged. Responses to both larval and adult worms have a characteristic T-helper type 2 profile, with activated mast cells in the gut mucosa, elevated levels of circulating immunoglobulin E, and eosinoophilia in the peripheral blood and local tissues, features also characteristic of type I hypersensitivity reactions. The longevity of adult hookworms is determined probably more by parasite genetics than by host immunity. However, many of the proteins released by the parasites seem to have immunomodulatory activity, presumably for self-protection. Advances in molecular biotechnology enable the identification and characterization of increasing numbers of these parasite molecules and should enhance our detailed understanding of the protective and pathogenetic mechanisms in hookworm infections

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A hookworm allergen which strongly resembles calreticulin

Cited by 64 publications

References 38 publications

Modulation of a Heterologous Immune Response by the Products ofAscaris suum

Modulation of a Heterologous Immune Response by the Products ofAscaris suum

Comparative Genomics of Gene Expression in the Parasitic and Free-Living Nematodes Strongyloides stercoralis and Caenorhabditis elegans

Immune Responses in Hookworm Infections

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