Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection

Wills‐Karp, Marsha; Rani, Reena; Dienger, Krista; Lewkowich, Ian P.; Fox, James G.; Perkins, Charles; Lewis, Lauren; Finkelman, Fred D.; Smith, Dirk E.; Bryce, Paul J.; Kurt-Jones, Evelyn A.; Wang, Yichen; Sivaprasad, Umasundari; Hershey, Gurjit K. Khurana; Herbert, De’Broski R.

doi:10.1084/jem.20110079

Cited by 187 publications

(189 citation statements)

References 82 publications

(141 reference statements)

Supporting

Mentioning

182

Contrasting

Unclassified

Order By: Relevance

“…More recently, we and others have shown that IL-33 is also produced from myeloid lineage cells within hours of pathogen exposure (8,14), which is consistent with a hypothesis that IL-33 functions as an "alarmin" that instructs adaptive immune responses (12). Our demonstration that IL-33KO mice were highly susceptible to both primary and secondary N. brasiliensis infection is consistent with reciprocal experiments that demonstrated IL-33 administration promoted the rapid expulsion of the gastrointestinal helminth T. muris (16).…”

Section: Discussionmentioning

confidence: 97%

“…At d 3 postinfection, IL-13-producing CD4 + T cells expand within the mediastinal lymph nodes (14), but this population does not accumulate within lung tissues until d 6 postinfection. IL-33 deficiency also significantly decreased both the percentage and number of lung IL-13 + CD4 + T cells during secondary immune responses, but IL-33 was not essential for expanding IL-4-producing CD4 + T cells.…”

Section: Discussionmentioning

confidence: 99%

“…We focused on how IL-33 regulated IL-13-producing lymphocytes (ILC2 and CD4 + T) within the lung, which is a major target organ of hookworm infection in both mice and humans (14). Within 3 d, the IL-13 + ILC2 population increased >100-fold in number through an IL-33-dependent mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…However, bioactive IL-33 can be generated following pro-IL-33 cleavage by other proteases such as neutrophil elastase and cathepsins, suggesting that bioactive IL-33 may be released into the extracellular environment (13). Indeed, mucosal damage caused by allergen or helminth infection elicits IL-33 production from epithelial cells, macrophages, and inflammatory dendritic cells (DCs) (14). Extracellular IL-33 exerts its biological activities, at least in part, through the suppressor of tumorigenicity (TI/ST2) receptor that signals through MyD88-mediated activation of MAP kinases and NF-κb (15 (18)(19)(20)(21).…”

mentioning

confidence: 99%

See 3 more Smart Citations

IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms

Hung

Lewkowich

Dawson

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

189

174

View full text Add to dashboard Cite

Parasitic helminths are a major cause of chronic human disease, affecting more than 3 billion people worldwide. Host protection against most parasitic helminths relies upon Type 2 cytokine production, but the mechanisms that regulate interleukin (IL) 4 and 13 production from CD4 + T helper 2 cells (T H 2) and innate lymphoid type 2 cells (ILC2s) remain incompletely understood. The epithelial cell-derived cytokines IL-25 and IL-33 promote Type 2 responses, but the extent of functional redundancy between these cytokines is unclear and whether Type 2 memory relies upon either IL-25 or IL-33 is unknown. Herein, we demonstrate a pivotal role for IL-33 in driving primary and anamnestic immunity against the rodent hookworm Nippostrongylus brasiliensis. IL-33-deficient mice have a selective defect in ILC2-derived IL-13 during both primary and secondary challenge infections but generate stronger canonical CD4 + T helper 2 cells responses (IL-4, IgE, mast cells, and basophils) than WT controls. Lack of IL-13 production in IL-33-deficient mice impairs resistin-like molecule beta (RELMβ) expression and eosinophil recruitment, which are two mechanisms that eliminate N. brasiliensis parasites from infected hosts. Thus, IL-33 is requisite for IL-13 but not IL-4-driven Type 2 responses during hookworm infection. mucosal immunity | gastrointestinal nematode | inflammation

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms

Hung

Lewkowich

Dawson

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

189

174

View full text Add to dashboard Cite

show abstract

“…In particular, TFF2 has been shown to be essential in the regulation of IL-33 release at mucosal surfaces (18). Increased susceptibility to Yersinia enterocolitica was found in TFF2-knockout mice, which died following infection (19).…”

mentioning

confidence: 99%

Host-derived, pore-forming toxin–like protein and trefoil factor complex protects the host against microbial infection

Xiang

Yan

Guo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

112

View full text Add to dashboard Cite

Aerolysins are virulence factors belonging to the bacterial β-poreforming toxin superfamily. Surprisingly, numerous aerolysin-like proteins exist in vertebrates, but their biological functions are unknown. βγ-CAT, a complex of an aerolysin-like protein subunit (two βγ-crystallin domains followed by an aerolysin pore-forming domain) and two trefoil factor subunits, has been identified in frogs (Bombina maxima) skin secretions. Here, we report the rich expression of this protein, in the frog blood and immune-related tissues, and the induction of its presence in peritoneal lavage by bacterial challenge. This phenomena raises the possibility of its involvement in antimicrobial infection. When βγ-CAT was administrated in a peritoneal infection model, it greatly accelerated bacterial clearance and increased the survival rate of both frogs and mice. Meanwhile, accelerated Interleukin-1β release and enhanced local leukocyte recruitments were determined, which may partially explain the robust and effective antimicrobial responses observed. The release of interleukin-1β was potently triggered by βγ-CAT from the frog peritoneal cells and murine macrophages in vitro. βγ-CAT was rapidly endocytosed and translocated to lysosomes, where it formed high molecular mass SDS-stable oligomers (>170 kDa). Lysosomal destabilization and cathepsin B release were detected, which may explain the activation of caspase-1 inflammasome and subsequent interleukin-1β maturation and release. To our knowledge, these results provide the first functional evidence of the ability of a host-derived aerolysin-like protein to counter microbial infection by eliciting rapid and effective host innate immune responses. The findings will also largely help to elucidate the possible involvement and action mechanisms of aerolysin-like proteins and/or trefoil factors widely existing in vertebrates in the host defense against pathogens.innate immunity | infectious disease | interleukin-1beta

show abstract

Dendritic Cells in Inflammatory Disease

Lambrecht

Guilliams

Hammad

2017

Inflammation - From Molecular and Cellular Mechanisms to the Clinic

View full text Add to dashboard Cite

Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection

Abstract: The repair protein trefoil factor 2 promotes Th2 responses to helminth infection and allergens in part by inducing IL-33.

Cited by 187 publications

References 82 publications

IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms

IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms

Host-derived, pore-forming toxin–like protein and trefoil factor complex protects the host against microbial infection

Dendritic Cells in Inflammatory Disease

Contact Info

Product

Resources

About