scholarly journals PGD2 and CRTH2 counteract Type 2 cytokine–elicited intestinal epithelial responses during helminth infection

2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Oyebola O. Oyesola ◽  
Michael T. Shanahan ◽  
Matt Kanke ◽  
Bridget M. Mooney ◽  
Lauren M. Webb ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Goblet Cell ◽  
Helminth Infection ◽  
Intestinal Helminth ◽  
Prostaglandin D2 ◽  
Intestinal Epithelial ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia ◽  
Small Intestinal

Type 2 inflammation is associated with epithelial cell responses, including goblet cell hyperplasia, that promote worm expulsion during intestinal helminth infection. How these epithelial responses are regulated remains incompletely understood. Here, we show that mice deficient in the prostaglandin D2 (PGD2) receptor CRTH2 and mice with CRTH2 deficiency only in nonhematopoietic cells exhibited enhanced worm clearance and intestinal goblet cell hyperplasia following infection with the helminth Nippostrongylus brasiliensis. Small intestinal stem, goblet, and tuft cells expressed CRTH2. CRTH2-deficient small intestinal organoids showed enhanced budding and terminal differentiation to the goblet cell lineage. During helminth infection or in organoids, PGD2 and CRTH2 down-regulated intestinal epithelial Il13ra1 expression and reversed Type 2 cytokine–mediated suppression of epithelial cell proliferation and promotion of goblet cell accumulation. These data show that the PGD2–CRTH2 pathway negatively regulates the Type 2 cytokine–driven epithelial program, revealing a mechanism that can temper the highly inflammatory effects of the anti-helminth response.

scholarly journals ILC2s mediate systemic innate protection by priming mucus production at distal mucosal sites

2019 ◽  
Vol 216 (12) ◽  
pp. 2714-2723 ◽  
Author(s):  
Laura Campbell ◽  
Matthew R. Hepworth ◽  
Jayde Whittingham-Dowd ◽  
Seona Thompson ◽  
Allison J. Bancroft ◽  
...  
Keyword(s):  
Goblet Cell ◽  
Helminth Infection ◽  
Host Immunity ◽  
Mucosal Barrier ◽  
Parasitic Nematodes ◽  
Cell Hyperplasia ◽  
Mucus Production ◽  
Mucin Production ◽  
Helminth Infections

Host immunity to parasitic nematodes requires the generation of a robust type 2 cytokine response, characterized by the production of interleukin 13 (IL-13), which drives expulsion. Here, we show that infection with helminths in the intestine also induces an ILC2-driven, IL-13–dependent goblet cell hyperplasia and increased production of mucins (Muc5b and Muc5ac) at distal sites, including the lungs and other mucosal barrier sites. Critically, we show that type 2 priming of lung tissue through increased mucin production inhibits the progression of a subsequent lung migratory helminth infection and limits its transit through the airways. These data show that infection by gastrointestinal-dwelling helminths induces a systemic innate mucin response that primes peripheral barrier sites for protection against subsequent secondary helminth infections. These data suggest that innate-driven priming of mucus barriers may have evolved to protect from subsequent infections with multiple helminth species, which occur naturally in endemic areas.

scholarly journals Intestinal helminth infection enhances bacteria-induced recruitment of neutrophils to the airspace

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shao Rong Long ◽  
Bernard B. Lanter ◽  
Michael A. Pazos ◽  
Hongmei Mou ◽  
Juliana Barrios ◽  
...  
Keyword(s):  
Structural Changes ◽  
Helminth Infection ◽  
Neutrophil Infiltration ◽  
Intestinal Helminth ◽  
Cell Hyperplasia ◽  
Heligmosomoides Polygyrus ◽  
Host Immune Responses ◽  
Th2 Cytokine ◽  
Helminth Infections

Abstract Intestinal helminth infections elicit Th2-type immunity, which influences host immune responses to additional threats, such as allergens, metabolic disease, and other pathogens. Th2 immunity involves a shift of the CD4+ T-cell population from type-0 to type-2 (Th2) with increased abundance of interleukin (IL)-4 and IL-13. This study sought to investigate if existing gut-restricted intestinal helminth infections impact bacterial-induced acute airway neutrophil recruitment. C57BL/6 mice were divided into four groups: uninfected; helminth-Heligmosomoides polygyrus infected; Pseudomonas aeruginosa infected; and coinfected. Mice infected with H. polygyrus were incubated for 2 weeks, followed by P. aeruginosa intranasal inoculation. Bronchial alveolar lavage, blood, and lung samples were analyzed. Interestingly, infection with gut-restricted helminths resulted in immunological and structural changes in the lung. These changes include increased lung CD4+ T cells, increased Th2 cytokine expression, and airway goblet cell hyperplasia. Furthermore, coinfected mice exhibited significantly more airspace neutrophil infiltration at 6 hours following P. aeruginosa infection and exhibited an improved rate of survival compared with bacterial infected alone. These results suggest that chronic helminth infection of the intestines can influence and enhance acute airway neutrophil responses to P. aeruginosa infection.

scholarly journals The development of an in vitro 3D model of goblet cell hyperplasia using MUC5AC expression and repeated whole aerosol exposures

2021 ◽  
Author(s):  
Linsey E. Haswell ◽  
David Smart ◽  
Tomasz Jaunky ◽  
Andrew Baxter ◽  
Simone Santopietro ◽  
...  
Keyword(s):  
Goblet Cell ◽  
3D Model ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia
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