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 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 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 Unusual presentations of a severe type 2 leprosy reaction mimicking sepsis induced by helminth infection

2021 ◽  
Vol 15 (7) ◽  
pp. e0009453
Author(s):  
Sri Linuwih Menaldi ◽  
Anastasia Asylia Dinakrisma ◽  
Hok Bing Thio ◽  
Iris Rengganis ◽  
Salma Oktaria
Keyword(s):  
Septic Shock ◽  
Unusual Case ◽  
Helminth Infection ◽  
Endoscopic Examination ◽  
Course Of Illness ◽  
Source Of Infection ◽  
Helminth Infections ◽  
History Of ◽  
Severe Type

We describe an unusual case of type 2 leprosy reaction (T2R) with septic shock–like features induced by helminth infection in a 31-year-old Moluccan male patient with a history of completed treatment of WHO multidrug therapy (MDT)–multibacillary (MB) regimen 2 years before admission. During the course of illness, the patient had numerous complications, including septic shock, anemia, and disseminated intravascular coagulation (DIC). Nevertheless, antibiotic therapies failed to give significant results, and the source of infection could not be identified. Helminth infection was subsequently revealed by endoscopic examination followed by parasitological culture. Resolution of symptoms and normal level of organ function–specific markers were resolved within 3 days following anthelmintic treatment. This report demonstrated the challenge in the diagnosis and treatment of severe T2R. Given that helminth infections may trigger severe T2R that mimics septic shock, health professionals need to be aware of this clinical presentation, especially in endemic regions of both diseases.

scholarly journals IL-4/IL-13 independent goblet cell hyperplasia in experimental helminth infections

2008 ◽  
Vol 9 (1) ◽  
pp. 11 ◽  
Author(s):  
Reece G Marillier ◽  
Chesney Michels ◽  
Elizabeth M Smith ◽  
Lizette CE Fick ◽  
Mosiuoa Leeto ◽  
...  
Keyword(s):  
Goblet Cell ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia ◽  
Helminth Infections

scholarly journals Macrophage Activation and Functions during Helminth Infection: Recent Advances from the Laboratory Mouse

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Marion Rolot ◽  
Benjamin G. Dewals
Keyword(s):  
Immune Responses ◽  
Helminth Infection ◽  
Laboratory Mouse ◽  
Alternative Activation ◽  
Recent Advances ◽  
Helminth Infections ◽  
Classically Activated Macrophages

Macrophages are highly plastic innate immune cells that adopt an important diversity of phenotypes in response to environmental cues. Helminth infections induce strong type 2 cell-mediated immune responses, characterized among other things by production of high levels of interleukin- (IL-) 4 and IL-13. Alternative activation of macrophages by IL-4 in vitro was described as an opposite phenotype of classically activated macrophages, but the in vivo reality is much more complex. Their exact activation state as well as the role of these cells and associated molecules in type 2 immune responses remains to be fully understood. We can take advantage of a variety of helminth models available, each of which have their own feature including life cycle, site of infection, or pathological mechanisms influencing macrophage biology. Here, we reviewed the recent advances from the laboratory mouse about macrophage origin, polarization, activation, and effector functions during parasitic helminth infection.

scholarly journals Activation of intestinal tuft cell-expressed Sucnr1 triggers type 2 immunity in the mouse small intestine

2018 ◽  
Vol 115 (21) ◽  
pp. 5552-5557 ◽  
Author(s):  
Weiwei Lei ◽  
Wenwen Ren ◽  
Makoto Ohmoto ◽  
Joseph F. Urban ◽  
Ichiro Matsumoto ◽  
...  
Keyword(s):  
Goblet Cell ◽  
Mucosal Immunity ◽  
Cell Activation ◽  
Nippostrongylus Brasiliensis ◽  
Infectious Agents ◽  
Cell Hyperplasia ◽  
Type 2 Immunity ◽  
Tuft Cell ◽  
Tuft Cells

The hallmark features of type 2 mucosal immunity include intestinal tuft and goblet cell expansion initiated by tuft cell activation. How infectious agents that induce type 2 mucosal immunity are detected by tuft cells is unknown. Published microarray analysis suggested that succinate receptor 1 (Sucnr1) is specifically expressed in tuft cells. Thus, we hypothesized that the succinate–Sucnr1 axis may be utilized by tuft cells to detect certain infectious agents. Here we confirmed that Sucnr1 is specifically expressed in intestinal tuft cells but not in other types of intestinal epithelial cells, and demonstrated that dietary succinate induces tuft and goblet cell hyperplasia via Sucnr1 and the tuft cell-expressed chemosensory signaling elements gustducin and Trpm5. Conventional mice with a genetic Sucnr1 deficiency (Sucnr1−/−) showed diminished immune responses to treatment with polyethylene glycol and streptomycin, which are known to enhance microbiota-derived succinate, but responded normally to inoculation with the parasitic worm Nippostrongylus brasiliensis that also produces succinate. Thus, Sucnr1 is required for microbiota-induced but not for a generalized worm-induced type 2 immunity.

scholarly journals Host- and Helminth-Derived Endocannabinoids That Have Effects on Host Immunity Are Generated during Infection

2018 ◽  
Vol 86 (11) ◽  
Author(s):  
Hashini M. Batugedara ◽  
Donovan Argueta ◽  
Jessica C. Jang ◽  
Dihong Lu ◽  
Marissa Macchietto ◽  
...  
Keyword(s):  
Helminth Infection ◽  
Parasite Burden ◽  
Endocannabinoid System ◽  
Bioinformatic Analysis ◽  
Host Immunity ◽  
Parasitic Nematodes ◽  
Nippostrongylus Brasiliensis ◽  
Helminth Parasites ◽  
Content Type ◽  
Intestinal Nematode

ABSTRACT Helminths have coevolved with their hosts, resulting in the development of specialized host immune mechanisms and parasite-specific regulatory products. Identification of new pathways that regulate helminth infection could provide a better understanding of host-helminth interaction and may identify new therapeutic targets for helminth infection. Here we identify the endocannabinoid system as a new mechanism that influences host immunity to helminths. Endocannabinoids are lipid-derived signaling molecules that control important physiologic processes, such as feeding behavior and metabolism. Following murine infection with Nippostrongylus brasiliensis, an intestinal nematode with a life cycle similar to that of hookworms, we observed increased levels of endocannabinoids (2-arachidonoylglycerol [2-AG] or anandamide [AEA]) and the endocannabinoid-like molecule oleoylethanolamine (OEA) in infected lung and intestine. To investigate endocannabinoid function in helminth infection, we employed pharmacological inhibitors of cannabinoid subtype receptors 1 and 2 (CB1R and CB2R). Compared to findings for vehicle-treated mice, inhibition of CB1R but not CB2R resulted in increased N. brasiliensis worm burden and egg output, associated with significantly decreased expression of the T helper type 2 cytokine interleukin 5 (IL-5) in intestinal tissue and splenocyte cultures. Strikingly, bioinformatic analysis of genomic and transcriptome sequencing (RNA-seq) data sets identified putative genes encoding endocannabinoid biosynthetic and degradative enzymes in many parasitic nematodes. To test the novel hypothesis that helminth parasites produce their own endocannabinoids, we measured endocannabinoid levels in N. brasiliensis by mass spectrometry and quantitative PCR and found that N. brasiliensis parasites produced endocannabinoids, especially at the infectious larval stage. To our knowledge, this is the first report of helminth- and host-derived endocannabinoids that promote host immune responses and reduce parasite burden.

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