Allergen presensitization drives an eosinophil-dependent arrest in lung-specific helminth development

Gazzinelli-Guimarães, Pedro Henrique; Prado, Rafael de Queiroz; Ricciardi, Alessandra; Bonne-Année, Sandra; Sciurba, Joshua; Karmele, Erik P.; Fujiwara, Ricardo Toshio; Nutman, Thomas B.

doi:10.1172/jci127963

Cited by 33 publications

(33 citation statements)

References 80 publications

(77 reference statements)

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“…brasiliensis infection, reducing intestinal parasite burden in an IL-33-, ILC-, IL-5- and eosinophil-dependent manner but independent of CD4 + T cells [ 39 ]. Direct evidence for a role of IL-33 in enhancing Th2-mediated attack of migrating parasitic nematodes in the lung arises from two other studies: IL-33 release triggered by house dust mite allergen administration reduced numbers of Ascaris lumbricoides larvae in the lung during subsequent infection [ 40 ], while H . polygyrus infection-induced IL-33 reduced N .…”

Section: Discussionmentioning

confidence: 99%

IL-33 facilitates rapid expulsion of the parasitic nematode Strongyloides ratti from the intestine via ILC2- and IL-9-driven mast cell activation

et al. 2020

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Parasitic helminths are sensed by the immune system via tissue-derived alarmins that promote the initiation of the appropriate type 2 immune responses. Here we establish the nuclear alarmin cytokine IL-33 as a non-redundant trigger of specifically IL-9-driven and mast cell-mediated immunity to the intestinal parasite Strongyloides ratti. Blockade of endogenous IL-33 using a helminth-derived IL-33 inhibitor elevated intestinal parasite burdens in the context of reduced mast cell activation while stabilization of endogenous IL-33 or application of recombinant IL-33 reciprocally reduced intestinal parasite burdens and increased mast cell activation. Using gene-deficient mice, we show that application of IL-33 triggered rapid mast cell-mediated expulsion of parasites directly in the intestine, independent of the adaptive immune system, basophils, eosinophils or Gr-1+ cells but dependent on functional IL-9 receptor and innate lymphoid cells (ILC). Thereby we connect the described axis of IL-33-mediated ILC2 expansion to the rapid initiation of IL-9-mediated and mast cell-driven intestinal anti-helminth immunity.

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Section: Discussionmentioning

confidence: 99%

IL-33 facilitates rapid expulsion of the parasitic nematode Strongyloides ratti from the intestine via ILC2- and IL-9-driven mast cell activation

et al. 2020

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“…To understand the role of HDM-induced antibodies in the allergen driven type-2 protective immune response to the parasite larvae [ 16 ], we examined the HDM-specific and Ascaris -specific antibody production over time ( Fig 1 ). Our data show that the HDM-sensitization induced strong systemic HDM-specific IgE levels ( Fig 1B–1D ) and HDM-specific IgG1 levels ( Fig 1E–1G ) in the HDM-sensitized groups (HDM + Ascaris - and HDM + Ascaris + ) at all-time points evaluated.…”

Section: Resultsmentioning

confidence: 99%

“…More recently, and based on immunological observations in humans [ 15 ] and in experimental models [ 16 ], it has been shown that allergic sensitization prior to acquisition of a helminth infection drives an eosinophil-rich type 2 immune response that has consequences for both pathology in the lung and for parasite development [ 16 ]. Indeed, this allergen-driven eosinophil-dominated type 2 response in the lungs led to a marked reduction in the number of Ascaris lung-stage larvae and to a profound developmental arrest in those larvae that survived.…”

Section: Introductionmentioning

confidence: 99%

House dust mite sensitization drives cross-reactive immune responses to homologous helminth proteins

et al. 2021

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The establishment of type 2 responses driven by allergic sensitization prior to exposure to helminth parasites has demonstrated how tissue-specific responses can protect against migrating larval stages, but, as a consequence, allow for immune-mediated, parasite/allergy-associated morbidity. In this way, whether helminth cross-reacting allergen-specific antibodies are produced and play a role during the helminth infection, or exacerbate the allergic outcome awaits elucidation. Thus, the main objective of the study was to investigate whether house dust mite (HDM) sensitization triggers allergen-specific antibodies that interact with Ascaris antigens and mediate antibody-dependent deleterious effects on these parasites as well as, to assess the capacity of cross-reactive helminth proteins to trigger allergic inflammation in house dust mite presensitized mice. Here, we show that the sensitization with HDM-extract drives marked IgE and IgG1 antibody responses that cross-react with Ascaris larval antigens. Proteomic analysis of Ascaris larval antigens recognized by these HDM-specific antibodies identified Ascaris tropomyosin and enolase as the 2 major HDM homologues based on high sequence and structural similarity. Moreover, the helminth tropomyosin could drive Type-2 associated pulmonary inflammation similar to HDM following HDM tropomyosin sensitization. The HDM-triggered IgE cross-reactive antibodies were found to be functional as they mediated immediate hypersensitivity responses in skin testing. Finally, we demonstrated that HDM sensitization in either B cells or FcγRIII alpha-chain deficient mice indicated that the allergen driven cell-mediated larval killing is not antibody-dependent. Taken together, our data suggest that aeroallergen sensitization drives helminth reactive antibodies through molecular and structural similarity between HDM and Ascaris antigens suggesting that cross-reactive immune responses help drive allergic inflammation.

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“…In a model in which mice are pre-sensitized to an allergen, Gazzinelli-Guimaraes et al show that subsequent infection with Ascaris lumbricoides presents with abrogated effect. This helminth preventive effect was associated with significantly increased IL-4, IL-13, and IL-33 in only those mice pre-sensitized with the allergen (Gazzinelli-Guimaraes et al, 2019). Detectable levels of eosinophil peroxidase as well as IL-5 and IL-13 are suggestive of the presence of an activated cohort of eosinophils in sensitized mice.…”

Section: Helminthsmentioning

confidence: 87%

“…Increased IL-33 is detected in serum from L. donovani patients Rostan et al, 2013;Takele et al, 2016 ST2 deficient mice demonstrate an ability to control parasite burden and reduced hepatomegaly and splenomegaly in an L. infantum model Khalid et al, 2017 Helminth Infection Helminth activity causes an increase in IL-33 mRNA expression Andronicos et al, 2012 Hymenolupis diminuta infection of mice deficient in mast cells have reduced IL-33 associated with increased parasite burden Hepworth et al, 2012;González et al, 2018 Mice pre-sensitized to an allergen prior to Ascaris lumbricoides infection demonstrate singificantly enhanced IL-33 expression and decreased parasite burden Gazzinelli-Guimaraes et al, 2019 IL-33 deficient mice cannot effectively recruit eosinophils or induce goblet cell hyperplasia Yasuda et al, 2012 IL-33 deficient mice cannot effectively recruit ILC2 cells resulting in increased parasite burden Yasuda et al, 2012Yasuda et al, , 2018 Heligmosomoides polygyrus exosomes inhibit IL-33/ST2 and M2 differentiation Buck et al, 2014;McSorley et al, 2014;Coakley et al, 2017 Ascaris suum exosomes likely inhibit IL-33 Hansen et al, 2019 Fasciola hepatica exosomes demonstrate an upregulation of IL-33 Finlay et al, 2016 combined with poor disease management practices, drug toxicity and a rise in parasitic resistance, have resulted in the high incidence and prevalence of parasitic infections seen in both developing and developed countries alike (Singh et al, 2019). For many years the scientific community has been working on developing novel strategies to prevent, contain and combat parasitic diseases.…”

Section: Role Of Il-33 Referencesmentioning

confidence: 99%

The IL-33/ST2 Axis in Immune Responses Against Parasitic Disease: Potential Therapeutic Applications

Ryan

Anderson

Volpedo

et al. 2020

Front. Cell. Infect. Microbiol.

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Parasitic infections pose a wide and varying threat globally, impacting over 25% of the global population with many more at risk of infection. These infections are comprised of, but not limited to, toxoplasmosis, malaria, leishmaniasis and any one of a wide variety of helminthic infections. While a great deal is understood about the adaptive immune response to each of these parasites, there remains a need to further elucidate the early innate immune response. Interleukin-33 is being revealed as one of the earliest players in the cytokine milieu responding to parasitic invasion, and as such has been given the name "alarmin." A nuclear cytokine, interleukin-33 is housed primarily within epithelial and fibroblastic tissues and is released upon cellular damage or death. Evidence has shown that interleukin-33 seems to play a crucial role in priming the immune system toward a strong T helper type 2 immune response, necessary in the clearance of some parasites, while disease exacerbating in the context of others. With the possibility of being a double-edged sword, a great deal remains to be seen in how interleukin-33 and its receptor ST2 are involved in the immune response different parasites elicit, and how those parasites may manipulate or evade this host mechanism. In this review article we compile the current cutting-edge research into the interleukin-33 response to toxoplasmosis, malaria, leishmania, and helminthic infection. Furthermore, we provide insight into directions interleukin-33 research may take in the future, potential immunotherapeutic applications of interleukin-33 modulation and how a better clarity of early innate immune system responses involving interleukin-33/ST2 signaling may be applied in development of much needed treatment options against parasitic invaders.

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Allergen presensitization drives an eosinophil-dependent arrest in lung-specific helminth development

Cited by 33 publications

References 80 publications

IL-33 facilitates rapid expulsion of the parasitic nematode Strongyloides ratti from the intestine via ILC2- and IL-9-driven mast cell activation

IL-33 facilitates rapid expulsion of the parasitic nematode Strongyloides ratti from the intestine via ILC2- and IL-9-driven mast cell activation

House dust mite sensitization drives cross-reactive immune responses to homologous helminth proteins

The IL-33/ST2 Axis in Immune Responses Against Parasitic Disease: Potential Therapeutic Applications

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