scholarly journals Context-dependent roles of B cells during intestinal helminth infection

2021 ◽  
Vol 15 (5) ◽  
pp. e0009340
Author(s):  
Aidil Zaini ◽  
Kim L. Good-Jacobson ◽  
Colby Zaph
Keyword(s):  
B Cells ◽  
Helminth Infection ◽  
Lymphoid Cells ◽  
Model Systems ◽  
Intestinal Helminth ◽  
Helminth Parasites ◽  
Potential Factors ◽  
New Perspective ◽  
Context Specific

The current approaches to reduce the burden of chronic helminth infections in endemic areas are adequate sanitation and periodic administration of deworming drugs. Yet, resistance against some deworming drugs and reinfection can still rapidly occur even after treatment. A vaccine against helminths would be an effective solution at preventing reinfection. However, vaccines against helminth parasites have yet to be successfully developed. While T helper cells and innate lymphoid cells have been established as important components of the protective type 2 response, the roles of B cells and antibodies remain the most controversial. Here, we review the roles of B cells during intestinal helminth infection. We discuss the potential factors that contribute to the context-specific roles for B cells in protection against diverse intestinal helminth parasite species, using evidence from well-defined murine model systems. Understanding the precise roles of B cells during resistance and susceptibility to helminth infection may offer a new perspective of type 2 protective immunity.

scholarly journals Innate and adaptive type 2 immune cell responses in genetically controlled resistance to intestinal helminth infection

2014 ◽  
Vol 92 (5) ◽  
pp. 436-448 ◽  
Author(s):  
Kara J Filbey ◽  
John R Grainger ◽  
Katherine A Smith ◽  
Louis Boon ◽  
Nico Rooijen ◽  
...  
Keyword(s):  
Helminth Infection ◽  
Immune Cell ◽  
Intestinal Helminth ◽  
Cell Responses

scholarly journals Parasite Proximity Drives the Expansion of Regulatory T Cells in Peyer's Patches following Intestinal Helminth Infection

2015 ◽  
Vol 83 (9) ◽  
pp. 3657-3665 ◽  
Author(s):  
Ilaria Mosconi ◽  
Lalit Kumar Dubey ◽  
Beatrice Volpe ◽  
Julia Esser-von Bieren ◽  
Mario M. Zaiss ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cytokine Production ◽  
Helminth Infection ◽  
Peyer's Patches ◽  
Intestinal Helminth ◽  
Peyer’S Patches ◽  
Intestinal Helminths ◽  
Content Type

Helminth infections are typically chronic in nature; however, the exact molecular mechanisms by which these parasites promote or thwart host immunity remain unclear. Worm expulsion requires the differentiation of CD4+T cells into Th2 cells, while regulatory T cells (Tregs) act to dampen the extent of the Th2 response. Priming of T cells requires drainage or capture of antigens within lymphoid tissues, and in the case of intestinal helminths, such sites include the mucosa-associated Peyer's patches (PPs) and the draining mesenteric lymph nodes (MLN). To gain insight into when and where the activation of the adaptive T cell response takes place following intestinal helminth infection, we analyzed Th2 and Treg responses in the PPs and MLN following infection with the murine intestinal helminthHeligmosomoides polygyrusbakeri. Protective Th2 responses were observed to be largely restricted to the MLN, while a greater expansion of Tregs occurred within the PPs. Interestingly, those PPs that formed a contact with the parasite showed the greatest degree of Treg expansion and no evidence of type 2 cytokine production, indicating that the parasite may secrete products that act in a local manner to selectively promote Treg expansion. This view was supported by the finding thatH. polygyrusbakerilarvae could promote Treg proliferationin vitro. Taken together, these data indicate that different degrees of Treg expansion and type 2 cytokine production occur within the PPs and MLN following infection with the intestinal helminthH. polygyrusbakeriand indicate that these organs exhibit differential responses following infection with intestinal helminths.

scholarly journals Group 2 Innate Lymphoid Cells Exhibit Tissue-Specific Dynamic Behaviour During Type 2 Immune Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Laurence S. C. Lok ◽  
Jennifer A. Walker ◽  
Helen E. Jolin ◽  
Seth T. Scanlon ◽  
Masaru Ishii ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Intestinal Mucosa ◽  
Dynamic Behaviour ◽  
Helminth Infection ◽  
Lymphoid Cells ◽  
Group 2

Group 2 innate lymphoid cells (ILC2s) are early effectors of mucosal type 2 immunity, producing cytokines such as interleukin (IL)-13 to mediate responses to helminth infection and allergen-induced inflammation. ILC2s are also present in lymph nodes (LNs) and can express molecules required for antigen presentation, but to date there are limited data on their dynamic behaviour. We used a CD2/IL-13 dual fluorescent reporter mouse for in vivo imaging of ILC2s and Th2 T cells in real time following a type 2 priming helminth infection or egg injection. After helminth challenge, we found that ILC2s were the main source of IL-13 in lymphoid organs (Peyer’s patches and peripheral LNs), and were located in T cell areas. Intravital imaging demonstrated an increase in IL-13+ ILC2 size and movement following helminth infection, but reduced duration of interactions with T cells compared with those in homeostasis. In contrast, in the intestinal mucosa, we observed an increase in ILC2-T cell interactions post-infection, including some of prolonged duration, as well as increased IL-13+ ILC2 movement. These data suggest that ILC2 activation enhances cell motility, with the potential to increase the area of distribution of cytokines to optimise the early generation of type 2 responses. The prolonged ILC2 interactions with T cells within the intestinal mucosa are consistent with the conclusion that contact-based T cell activation may occur within inflamed tissues rather than lymphoid organs. Our findings have important implications for our understanding of the in vivo biology of ILC2s and the way in which these cells facilitate adaptive immune responses.

scholarly journals Concerted IL-25R and IL-4Rα signaling drive innate type 2 effector immunity for optimal helminth expulsion

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Katherine A Smith ◽  
Stephan Löser ◽  
Fumi Varyani ◽  
Yvonne Harcus ◽  
Henry J McSorley ◽  
...  
Keyword(s):  
Chronic Infection ◽  
Lymphoid Cells ◽  
Helminth Parasites ◽  
Wild Type ◽  
Heligmosomoides Polygyrus ◽  
Innate Effector ◽  
Interleukin 25 ◽  
Deficient Mice

Interleukin 25 (IL-25) is a major 'alarmin' cytokine, capable of initiating and amplifying the type immune response to helminth parasites. However, its role in the later effector phase of clearing chronic infection remains unclear. The helminth Heligmosomoides polygyrus establishes long-term infections in susceptible C57BL/6 mice, but is slowly expelled in BALB/c mice from day 14 onwards. We noted that IL-25R (Il17rb)-deficient BALB/c mice were unable to expel parasites despite type 2 immune activation comparable to the wild-type. We then established that in C57BL/6 mice, IL-25 adminstered late in infection (days 14–17) drove immunity. Moreover, when IL-25 and IL-4 were delivered to Rag1-deficient mice, the combination resulted in near complete expulsion of the parasite, even following administration of an anti-CD90 antibody to deplete innate lymphoid cells (ILCs). Hence, effective anti-helminth immunity during chronic infection requires an innate effector cell population that is synergistically activated by the combination of IL-4Rα and IL-25R signaling.

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.

Levels of helminth infection in the flat lizard Tropidurus semitaeniatus from north-eastern Brazil

2015 ◽  
Vol 90 (6) ◽  
pp. 779-783 ◽  
Author(s):  
C.H. Bezerra ◽  
R.W. Ávila ◽  
D.C. Passos ◽  
D. Zanchi-Silva ◽  
C.A.B. Galdino
Keyword(s):  
Body Size ◽  
Helminth Infection ◽  
Helminth Species ◽  
Intestinal Helminth ◽  
Helminth Parasites ◽  
Intestinal Nematode ◽  
Eastern Brazil ◽  
Host Sex ◽  
North Eastern ◽  
First Time

AbstractParasites represent a great, unknown component of animal biodiversity. Recent efforts have begun to uncover patterns of infection by helminth parasites in several Neotropical lizards. The present study reports, for the first time, levels of helminth infection in a population of the flat lizard Tropidurus semitaeniatus. One hundred and thirty-nine lizards were examined and evidence of five intestinal helminth species was found, comprising four species of nematodes, one species of cestode and an unidentified encysted larval nematode. The most frequently occurring species was the intestinal nematode Parapharyngodon alvarengai, which did not exhibit differences in prevalence and intensity of infection relative to host sex or age/body size. Furthermore, helminth species richness was not related to host body size.

scholarly journals Inhibition of miR-99a-5p prevents allergen-driven airway exacerbations without compromising type-2 memory responses in the intestine following helminth infection

2021 ◽  
Author(s):  
Lewis Entwistle ◽  
Helena Aegerter ◽  
Stephanie Czieso ◽  
Eleni Amaniti ◽  
Riccardo Guidi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Helminth Infection ◽  
Smooth Muscle Contraction ◽  
Therapeutic Interventions ◽  
Transcriptional Analysis ◽  
Intestinal Helminth ◽  
Heligmosomoides Polygyrus ◽  
Minimal Impact ◽  
Acute Exacerbations

AbstractAcute exacerbations (AE) of asthma, remain one of the biggest concerns for patients living with asthma. As such, identifying the causes, the molecular mechanisms involved and new therapeutic interventions to prevent AE is a high priority. Immunity to intestinal helminths involves the reactivation of type-2 immune responses leading to smooth muscle contraction and mucus hypersecretion–physiological processes very similar to acute exacerbations in the airways following allergen exposure. In this study, we employed a murine model of intestinal helminth infection, using Heligmosomoides polygyrus, to identify miRNAs during active expulsion, as a system for the identification of miRNAs that may contribute to AE in the airways. Concomitant with type-2 immunity and expulsion of H. polygyrus, we identified miR-99a-5p, miR-148a-3p and miR-155-5p that were differentially regulated. Systemic inhibition of these miRNAs, alone or in combination, had minimal impact on expulsion of H. polygyrus, but inhibition of miR-99a-5p or miR-155-5p significantly reduced house dust mite (HDM)-driven acute inflammation, modelling human acute exacerbations. Immunological, pathological and transcriptional analysis identified that miR-155-5p or miR-99a-5p contribute significantly to HDM-driven AE and that transient inhibition of these miRNAs may provide relief from allergen-driven AE, without compromising anti-helminth immunity in the gut.

scholarly journals The role of rare innate immune cells in Type 2 immune activation against parasitic helminths

Parasitology ◽  
2017 ◽  
Vol 144 (10) ◽  
pp. 1288-1301 ◽  
Author(s):  
LAUREN M. WEBB ◽  
ELIA D. TAIT WOJNO
Keyword(s):  
Immune Cells ◽  
Low Frequency ◽  
Cell Types ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Innate Immune Cells ◽  
Helminth Parasites ◽  
Parasitic Helminths ◽  
Group 2

SUMMARYThe complexity of helminth macroparasites is reflected in the intricate network of host cell types that participate in the Type 2 immune response needed to battle these organisms. In this context, adaptive T helper 2 cells and the Type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 have been the focus of research for years, but recent work has demonstrated that the innate immune system plays an essential role. Some innate immune cells that promote Type 2 immunity are relatively abundant, such as macrophages and eosinophils. However, we now appreciate that more rare cell types including group 2 innate lymphoid cells, basophils, mast cells and dendritic cells make significant contributions to these responses. These cells are found at low frequency but they are specialized to their roles – located at sites such as the skin, lung and gut, where the host combats helminth parasites. These cells respond rapidly and robustly to worm antigens and worm-induced damage to produce essential cytokines, chemokines, eicosanoids and histamine to activate damaged epithelium and to recruit other effectors. Thus, a greater understanding of how these cells operate is essential to understand how the host protects itself during helminth infection.

scholarly journals The ChAT-acetylcholine pathway promotes group 2 innate lymphoid cell responses and anti-helminth immunity

2021 ◽  
Vol 6 (57) ◽  
pp. eabe3218
Author(s):  
Coco Chu ◽  
Christopher N. Parkhurst ◽  
Wen Zhang ◽  
Lei Zhou ◽  
Hiroshi Yano ◽  
...  
Keyword(s):  
Acetylcholine Receptors ◽  
Helminth Infection ◽  
Allergic Inflammation ◽  
Lymphoid Cells ◽  
Nippostrongylus Brasiliensis ◽  
Interleukin 5 ◽  
Helminth Infections ◽  
Group 2

Group 2 innate lymphoid cells (ILC2s) reside in multiple tissues, including lymphoid organs and barrier surfaces, and secrete type 2 cytokines including interleukin-5 (IL-5), IL-9, and IL-13. These cells participate in multiple physiological processes including allergic inflammation, tissue repair, metabolic homeostasis, and host defense against helminth infections. Recent studies indicate that neurotransmitters and neuropeptides can play an important role in regulating ILC2 responses; however, the mechanisms that underlie these processes in vivo remain incompletely defined. Here, we identify that activated ILC2s up-regulate choline acetyltransferase (ChAT)—the enzyme responsible for the biosynthesis of acetylcholine (ACh)—after infection with the helminth parasite Nippostrongylus brasiliensis or treatment with alarmins or cytokines including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). ILC2s also express acetylcholine receptors (AChRs), and ACh administration promotes ILC2 cytokine production and elicits expulsion of helminth infection. In accordance with this, ChAT deficiency in ILC2s leads to defective ILC2 responses and impaired immunity against helminth infection. Together, these results reveal a previously unrecognized role of the ChAT-ACh pathway in promoting type 2 innate immunity to helminth infection.

scholarly journals Group 2 Innate Lymphoid Cells (ILC2): Type 2 Immunity and Helminth Immunity

2019 ◽  
Vol 20 (9) ◽  
pp. 2276 ◽  
Author(s):  
De’Broski Herbert ◽  
Bonnie Douglas ◽  
Kelly Zullo
Keyword(s):  
Cell Lineage ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Helminth Parasites ◽  
Cell Recruitment ◽  
Distinct Cell ◽  
Health And Disease ◽  
Group 2 ◽  
Unique Cell

Group 2 innate lymphoid cells (ILC2) have emerged as a major component of type 2 inflammation in mice and humans. ILC2 secrete large amounts of interleukins 5 and 13, which are largely responsible for host protective immunity against helminth parasites because these cytokines induce profound changes in host physiology that include: goblet cell metaplasia, mucus accumulation, smooth muscle hypercontractility, eosinophil and mast cell recruitment, and alternative macrophage activation (M2). This review covers the initial recognition of ILC2 as a distinct cell lineage, the key studies that established their biological importance, particularly in helminth infection, and the new directions that are likely to be the focus of emerging work that further explores this unique cell population in the context of health and disease.

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