scholarly journals Heterogeneous Tfh cell populations that develop during enteric helminth infection predict the quality of type 2 protective response

2021 ◽  
Author(s):  
Aidil Zaini ◽  
Lennard Dalit ◽  
Amania A. Sheikh ◽  
Daniel Thiele ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Helminth Infection ◽  
Protective Role ◽  
Chromatin Accessibility ◽  
Cell Populations ◽  
Trichuris Muris ◽  
Cell Responses ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Helminth Infections

T follicular helper (Tfh) cells are an important component of the germinal centre (GC)-mediated humoral immunity. Yet, how regulation of Tfh-GC responses impacts on effective responses to helminth infection are poorly understood. Here we show that chronic helminth Trichuris muris infection fails to induce Tfh-GC B cell responses, with Tfh cells expressing T-bet and IFN-γ. In contrast, Tfh cells that express GATA-3 and IL-4 dominate responses to an acute, resolving infection. Accordingly, heightened expression and increased chromatin accessibility of Th1- and Th2 cell-associated genes is observed in chronic and acute induced Tfh cells, respectively. However, both acute and chronic Tfh cell populations retained the capacity to produce IL-21 in spite of the Th-biased response. Blockade of Tfh-GC interactions impaired type 2 immunity, highlighting the protective role of GC-dependent Th2-like Tfh cell responses against helminths. Collectively, these results provide new insights into the protective roles of Tfh-GC responses and identify distinct transcriptional and epigenetic features of Tfh cells that emerge during resolving or chronic helminth infections.

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 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 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 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 Regulation of Intrinsic and Bystander T Follicular Helper Cell Differentiation and Autoimmunity by Tsc1

2021 ◽  
Vol 12 ◽  
Author(s):  
Shimeng Zhang ◽  
Lei Li ◽  
Danli Xie ◽  
Srija Reddy ◽  
John W. Sleasman ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Immune Responses ◽  
B Cell ◽  
Regulatory Cells ◽  
Wild Type ◽  
Autoantibody Production ◽  
Cell Responses ◽  
Tfh Cells ◽  
Follicular Helper

T Follicular helper (Tfh) cells promote germinal center (GC) B cell responses to develop effective humoral immunity against pathogens. However, dysregulated Tfh cells can also trigger autoantibody production and the development of autoimmune diseases. We report here that Tsc1, a regulator for mTOR signaling, plays differential roles in Tfh cell/GC B cell responses in the steady state and in immune responses to antigen immunization. In the steady state, Tsc1 in T cells intrinsically suppresses spontaneous GC-Tfh cell differentiation and subsequent GC-B cell formation and autoantibody production. In immune responses to antigen immunization, Tsc1 in T cells is required for efficient GC-Tfh cell expansion, GC-B cell induction, and antigen-specific antibody responses, at least in part via promoting GC-Tfh cell mitochondrial integrity and survival. Interestingly, in mixed bone marrow chimeric mice reconstituted with both wild-type and T cell-specific Tsc1-deficient bone marrow cells, Tsc1 deficiency leads to enhanced GC-Tfh cell differentiation of wild-type CD4 T cells and increased accumulation of wild-type T regulatory cells and T follicular regulatory cells. Such bystander GC-Tfh cell differentiation suggests a potential mechanism that could trigger self-reactive GC-Tfh cell/GC responses and autoimmunity via neighboring GC-Tfh cells.

scholarly journals Frontiers of Autoantibodies in Autoimmune Disorders: Crosstalk Between Tfh/Tfr and Regulatory B Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Tingting Ding ◽  
Rui Su ◽  
Ruihe Wu ◽  
Hongwei Xue ◽  
Yanyan Wang ◽  
...  
Keyword(s):  
B Cells ◽  
Autoimmune Diseases ◽  
Treg Cells ◽  
Regulatory B Cells ◽  
Cellular Mechanisms ◽  
Autoantibody Production ◽  
Cell Responses ◽  
Tfh Cells ◽  
Follicular Helper

Balance of Tfh/Tfr cell is critically important for the maintenance of immune tolerance, as evidenced by the fact that T follicular helper (Tfh) cells are central to the autoantibodies generation through providing necessary help for germinal center (GC) B cells, whereas T follicular regulatory (Tfr) cells significantly inhibit autoimmune inflammation process through restraining Tfh cell responses. However, signals underlying the regulation of Tfh and Tfr cells are largely undefined. Regulatory B cells (Bregs) is a heterogeneous subpopulation of B cells with immunosuppressive function. Considerable advances have been made in their functions to produce anti‐inflammatory cytokines and to regulate Th17, Th1, and Treg cells in autoimmune diseases. The recent identification of their correlations with dysregulated Tfr/Tfh cells and autoantibody production makes Bregs an important checkpoint in GC response. Bregs exert profound impacts on the differentiation, function, and distribution of Tfh and Tfr cells in the immune microenvironment. Thus, unraveling mechanistic information on Tfh-Breg and Tfr-Breg interactions will inspire novel implications for the establishment of homeostasis and prevention of autoantibodies in diverse diseases. This review summarizes the dysregulation of Tfh/Tfr cells in autoimmune diseases with a focus on the emerging role of Bregs in regulating the balance between Tfh and Tfr cells. The previously unsuspected crosstalk between Bregs and Tfh/Tfr cells will be beneficial to understand the cellular mechanisms of autoantibody production and evoke a revolution in immunotherapy for autoimmune diseases.

scholarly journals IL-4–producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells

2009 ◽  
Vol 206 (5) ◽  
pp. 1001-1007 ◽  
Author(s):  
Irah L. King ◽  
Markus Mohrs
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Cd4 T Cells ◽  
Helminth Infection ◽  
Th2 Cells ◽  
Mesenteric Lymph Nodes ◽  
Th2 Response ◽  
Tfh Cells ◽  
Follicular Helper

Interleukin (IL)-4 is the quintessential T helper type 2 (Th2) cytokine produced by CD4+ T cells in response to helminth infection. IL-4 not only promotes the differentiation of Th2 cells but is also critical for immunoglobulin (Ig) G1 and IgE isotype-switched antibody responses. Despite the IL-4–mediated link between Th2 cells and B lymphocytes, the location of IL-4–producing T cells in the lymph nodes is currently unclear. Using IL-4 dual reporter mice, we examined the Th2 response and IL-4 production in the draining mesenteric lymph nodes during infection with the enteric nematode Heligmosomoides polygyrus. We show that although IL-4–competent Th2 cells are found throughout the B and T cell areas, IL-4–producing Th2 cells are restricted to the B cell follicles and associate with germinal centers. Consistent with their localization, IL-4 producers express high levels of CXCR5, ICOS, PD-1, IL-21, and BCL-6, a phenotype characteristic of T follicular helper (Tfh) cells. Although IL-4 was dispensable for the generation of Th2 and Tfh cells, its deletion resulted in defective B cell expansion and maturation. Our report reveals the compartmentalization of Th2 priming and IL-4 production in the lymph nodes during infection, and identifies Tfh cells as the dominant source of IL-4 in vivo.

scholarly journals Neoantigen driven B cell and CD4+ T follicular helper cell collaboration promotes robust anti-tumor CD8+ T cell responses

2020 ◽  
Author(s):  
Can Cui ◽  
Jiawei Wang ◽  
Ping-Min Chen ◽  
Kelli A. Connolly ◽  
Martina Damo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Interactions ◽  
Tumor Control ◽  
Cell Responses ◽  
Tfh Cells ◽  
Follicular Helper ◽  
T Follicular Helper Cell

AbstractCD4+ T follicular helper (TFH) cells provide help to B cells, which is critical for germinal center (GC) formation, but the importance of TFH-B cell interactions in cancer is unclear. We found TFH cells correlated with GC B cells and with prolonged survival of lung adenocarcinoma (LUAD) patients. To investigate further, we developed an LUAD model, in which tumor cells expressed B-cell- and T-cell-recognized neoantigens. Interactions between tumor-specific TFH and GC B cells were necessary for tumor control, as were effector CD8+ T cells. The latter were reduced in the absence of T cell-B cell interactions or the IL-21 receptor. IL-21 was produced primarily by TFH cells, development of which required B cells. Moreover, development of tumor-specific TFH cell-responses was also reliant upon tumors that expressed B-cell-recognized neoantigens. Thus, tumor-neoantigens themselves can control the fate decisions of tumor-specific CD4+ T cells by facilitating interactions with tumor-specific B cells.Abstract Figure

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.

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