Interleukin-13 Receptor α1-Dependent Responses in the Intestine Are Critical to Parasite Clearance

Sun, Rex; Urban, Joseph F.; Notari, Luigi; Vanuytsel, Tim; Madden, Kathleen B.; Bohl, Jennifer A.; Ramalingam, Thirumalai R.; Wynn, Thomas A.; Zhao, Aiping; Shea‐Donohue, Terez

doi:10.1128/iai.00990-15

Cited by 21 publications

(18 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whether these claudin-2-dependent increases in water efflux simply wash away adherent C. rodentium or, alternatively, have some other effects on the microbiome has not been addressed here but could be an interesting question. Regardless of the mechanism, the claudin-2-dependent pathogen clearance described here is distinct from IL-13-dependent helminth expulsion, where claudin-2 upregulation occurs but does not contribute significantly to host defense (Sun et al, 2016). …”

Section: Discussionmentioning

confidence: 96%

IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance

Tsai

Zhang

et al. 2017

Cell Host & Microbe

196

200

View full text Add to dashboard Cite

SUMMARY Diarrhea is a host response to enteric pathogens, but its impact on pathogenesis remains poorly defined. By infecting mice with the attaching and effacing bacteria Citrobacter rodentium, we defined the mechanisms and contributions of diarrhea and intestinal barrier loss to host defense. Increased permeability occurred within 2 days of infection and coincided with IL-22-dependent upregulation of the epithelial tight junction protein claudin-2. Permeability increases were limited to small molecules, as expected for the paracellular water and Na+ channel formed by claudin-2. Relative to wildtype, claudin-2-deficient mice experienced severe disease, including increased mucosal colonization by C. rodentium, prolonged pathogen shedding, exaggerated cytokine responses, and greater tissue injury. Conversely, transgenic claudin-2 overexpression reduced disease severity. Chemically-induced osmotic diarrhea reduced colitis severity and C. rodentium burden in claudin-2 deficient, but not transgenic, mice, demonstrating that claudin-2-mediated protection is the result of enhanced water efflux. Thus, IL-22-induced claudin-2 upregulation drives diarrhea and pathogen clearance.

show abstract

Section: Discussionmentioning

confidence: 96%

IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance

Tsai

Zhang

et al. 2017

Cell Host & Microbe

196

200

View full text Add to dashboard Cite

show abstract

“…68 The drop in TER in secondary infections with H. polygyrus, was accompanied by a small increase in the epithelial expression of the pore-forming claudin-2, and the barrier defect was absent in IL-13Ra1 ¡/¡ mice. 69 Increased IL-13 production following infection with helminths can be from innate 70 or adaptive immune cells, 71 and while IL-13 has been shown to directly decrease the barrier function of epithelial monolayers in vitro, 24,72 it is unclear if helminth-evoked IL-13 targets the epithelium directly or via other immunoregulatory activities.…”

Section: Increased Epithelial Permeability Triggered By Infection Witmentioning

confidence: 99%

Helminths and intestinal barrier function

2017

View full text Add to dashboard Cite

Approximately one-sixth of the worlds' population is infected with helminths and this class of parasite takes a major toll on domestic livestock. The majority of species of parasitic helminth that infect mammals live in the gut (the only niche for tapeworms) where they contact the hosts' epithelial cells. Here, the helminth-intestinal epithelial interface is reviewed in terms of the impact on, and regulation of epithelial barrier function, both intrinsic (epithelial permeability) and extrinsic (mucin, bacterial peptides, commensal bacteria) elements of the barrier. The data available on direct effects of helminths on epithelial permeability are scant, fragmentary and pales in comparison with knowledge of mobilization of immune reactions and effector cells in response to helminth parasites and how these impact intestinal barrier function. The interaction of helminth-host and helminthhost-bacteria is an important determinant of gut form and function and precisely defining these interactions will radically alter our understanding of normal gut physiology and pathophysiological reactions, revealing new approaches to infection with parasitic helminths, bacterial pathogens and idiopathic auto-inflammatory disease.

show abstract

“…Interestingly, PBV smooth muscle hyperplasia was equivalent between WT and RELM-β null mice (data not shown) indicating that sustained AHR in KO mice may not be due to smooth muscle cell hyperplasia. Whilst IL-13 has been shown to induce RELM-β production 32 , a possible feedback regulation on IL-13 by RELM-β has not been previously demonstrated. Since IL-13 can influence airway inflammation, hyperresponsiveness, fibrosis, and fibroblast functions 57 – 59 , these characteristics may have been heightened due to Il13 overexpression in Retnlb −/− mice, thereby suggesting a novel function for RELM-β as a negative regulator of IL-13 in asthma.…”

Section: Discussionmentioning

confidence: 90%

“…IL-13 is a key T H 2 cytokine known to have functions in AHR and airway remodelling, among others, during allergy. IL-13 promotes RELM-β in the gut 32 possibly through enhancement of GC metaplasia and also induces RELM-β production by airway epithelial cells 16 . However, we found that Il13 was highly expressed in mice deficient in Retnlb compared to WT controls (Fig.…”

Section: Resultsmentioning

confidence: 99%

Chronic features of allergic asthma are enhanced in the absence of resistin-like molecule-beta

LeMessurier

Palipane

Tiwary

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Asthma is characterized by inflammation and architectural changes in the lungs. A number of immune cells and mediators are recognized as initiators of asthma, although therapeutics based on these are not always effective. The multifaceted nature of this syndrome necessitate continued exploration of immunomodulators that may play a role in pathogenesis. We investigated the role of resistin-like molecule-beta (RELM-β), a gut antibacterial, in the development and pathogenesis of Aspergillus-induced allergic airways disease. Age and gender matched C57BL/6J and Retnlb−/− mice rendered allergic to Aspergillus fumigatus were used to measure canonical markers of allergic asthma at early and late time points. Inflammatory cells in airways were similar, although Retnlb−/− mice had reduced tissue inflammation. The absence of RELM-β elevated serum IgA and pro-inflammatory cytokines in the lungs at homeostasis. Markers of chronic disease including goblet cell numbers, Muc genes, airway wall remodelling, and hyperresponsiveness were greater in the absence RELM-β. Specific inflammatory mediators important in antimicrobial defence in allergic asthma were also increased in the absence of RELM-β. These data suggest that while characteristics of allergic asthma develop in the absence of RELM-β, that RELM-β may reduce the development of chronic markers of allergic airways disease.

show abstract

Interleukin-13 Receptor α1-Dependent Responses in the Intestine Are Critical to Parasite Clearance

Cited by 21 publications

References 40 publications

IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance

IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance

Helminths and intestinal barrier function

Chronic features of allergic asthma are enhanced in the absence of resistin-like molecule-beta

Contact Info

Product

Resources

About