Rapid induction of IgE responses to a worm cysteine protease during murine pre-patent schistosome infection

Abstract

BackgroundDuring the pre-patent stage of infection, juvenile Schistosoma blood flukes co-opt signals from the adaptive immune system to facilitate parasite development, but the types of responses that are induced at this early stage of infection, and the parasite antigens they target, have not been characterized.ResultsThrough analysis of experimental pre-patent infections, we show that the S. mansoni cysteine protease SmCB1 is rapidly targeted by an antigen-specific IgE response. The induction of this response is independent of schistosome eggs as infection with male or female worms alone also induced SmCB1-specific IgE. We also show that the SmCB1-specific IgE response is dependent on cognate CD4+ T cell help and IL-4, suggesting that pre-patent Th2 responses provide T cell help for the SmCB1-specific IgE response. Finally, exposed human subjects also produced IgE against SmCB1.ConclusionsOur data demonstrate that, like eggs, schistosome worms also induce functional type 2 responses and that a parasite cysteine protease is an inducer of type 2 responses during the early stages of schistosome infection.

Schistosoma mansoni Venom Allergen Like Proteins Present Differential Allergic Responses in a Murine Model of Airway Inflammation

“…Moreover, the induction of CD4 + T cells, specific IgE and basophils that produce IL-4 in response to worm antigens (e.g. SmCB1 – Cathepsin B) have also been described in this phase [39]. Finally, there is increasing evidence that excretory/secretory molecules from schistosome larvae can stimulate a mixed T helper response in the skin, with evidence of both Th1 and Th2 skewed responses at the site of infection [40].…”

Regulation of Innate Responses during Pre-patent Schistosome Infection Provides an Immune Environment Permissive for Parasite Development

“…In previous studies, we showed that, prior to the onset of egg production, pre-patent schistosome infection results in the rapid establishment of a T H 2 response [10], [11], where CD4 + T cells produce significant quantities of IL-4 in response to worm antigens [10]. As IL-4 is a type 2 cytokine that regulates pro-inflammatory signals, including IL-1β [33]–[35], we hypothesized that IL-4 may represent the adaptive mechanism by which IL-1β is regulated in wild type mice.…”

“…M2 macrophages have also been shown to limit brain tissue pathology in a murine model of neurocysticercosis [59] [60], where decreased numbers of brain M2 macrophages in Mesocestoides corti -infected mice was shown to result in increased disease severity. The induction of systemic T H 2 responses has been shown to occur early in S. mansoni infection [10], [11]. Indeed, multiple exposure of skin to invading cercariae, as likely occurs under field conditions, has been shown to be sufficient to induce M2 conditioning of macrophages at the site of infection [61].…”

“…In schistosomaisis, T H 2 responses against parasite antigens are required for the formation of protective granulomas around parasite eggs [8], [9]. T H 2 responses to worm antigens develop even before the onset of egg production [10], [11] and there is evidence that this immune priming by the developing worms is necessary to ensure proper T H 2 granuloma formation [12]. T H 2 responses are also critical for host survival after egg production begins, as lack of IL-4 signaling leads to severe disease and early mortality as a result of excessive pro-inflammatory processes [8], [9], [13]–[15].…”

Excretion/secretion products from Schistosoma mansoni adults, eggs and schistosomula have unique peptidase specificity profiles

“…Schistosoma peptidases (a.k.a. proteases or proteolytic enzymes) are vital to successful parasitism, and facilitate invasion of the host, digestion of host proteins, reproduction, modulation of the host’s physiology [11–19] and immune response [14, 20]. Interference with these mechanisms by specific vaccines [21, 22] or drugs may provide therapeutic benefits.…”