scholarly journals The Framework for Human Host Immune Responses to Four Types of Parasitic Infections and Relevant Key JAK/STAT Signaling

2021 ◽  
Vol 22 (24) ◽  
pp. 13310
Author(s):  
Tsung-Han Wen ◽  
Kuo-Wang Tsai ◽  
Yan-Jun Wu ◽  
Min-Tser Liao ◽  
Kuo-Cheng Lu ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Mast Cells ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Interleukin 4 ◽  
Parasitic Infections ◽  
Stat Signaling

The human host immune responses to parasitic infections are complex. They can be categorized into four immunological pathways mounted against four types of parasitic infections. For intracellular protozoa, the eradicable host immunological pathway is TH1 immunity involving macrophages (M1), interferon gamma (IFNγ) CD4 T cells, innate lymphoid cells 1 (NKp44+ ILC1), CD8 T cells (Effector-Memory4, EM4), invariant natural killer T cells 1 (iNKT1) cells, and immunoglobulin G3 (IgG3) B cells. For intracellular protozoa, the tolerable host immunological pathway is TH1-like immunity involving macrophages (M2), interferon gamma (IFNγ)/TGFβ CD4 T cells, innate lymphoid cells 1 (NKp44- ILC1), CD8 T cells (EM3), invariant natural killer T 1 (iNKT1) cells, and immunoglobulin A1 (IgA1) B cells. For free-living extracellular protozoa, the eradicable host immunological pathway is TH22 immunity involving neutrophils (N1), interleukin-22 CD4 T cells, innate lymphoid cells 3 (NCR+ ILC3), iNKT17 cells, and IgG2 B cells. For free-living extracellular protozoa, the tolerable host immunological pathway is TH17 immunity involving neutrophils (N2), interleukin-17 CD4 T cells, innate lymphoid cells 3 (NCR- ILC3), iNKT17 cells, and IgA2 B cells. For endoparasites (helminths), the eradicable host immunological pathway is TH2a immunity with inflammatory eosinophils (iEOS), interleukin-5/interleukin-4 CD4 T cells, interleukin-25 induced inflammatory innate lymphoid cells 2 (iILC2), tryptase-positive mast cells (MCt), iNKT2 cells, and IgG4 B cells. For ectoparasites (parasitic insects and arachnids), the eradicable host immunological pathway is TH2b immunity with inflammatory basophils, chymase- and tryptase-positive mast cells (MCct), interleukin-3/interleukin-4 CD4 T cells, interleukin-33 induced nature innate lymphoid cells 2 (nILC2), iNKT2 cells, and immunoglobulin E (IgE) B cells. The tolerable host immunity against ectoparasites and endoparasites is TH9 immunity with regulatory eosinophils, regulatory basophils, interleukin-9 mast cells (MMC9), thymic stromal lymphopoietin induced innate lymphoid cells 2, interleukin-9 CD4 T cells, iNKT2 cells, and IgA2 B cells. In addition, specific transcription factors important for specific immune responses were listed. This JAK/STAT signaling is key to controlling or inducing different immunological pathways. In sum, Tfh is related to STAT5β, and BCL6 expression. Treg is related to STAT5α, STAT5β, and FOXP3. TH1 immunity is related to STAT1α, STAT4, and T-bet. TH2a immunity is related to STAT6, STAT1α, GATA1, and GATA3. TH2b immunity is related to STAT6, STAT3, GATA2, and GATA3. TH22 immunity is associated with both STAT3α and AHR. THαβ immunity is related to STAT1α, STAT1β, STAT2, STAT3β, and ISGF. TH1-like immunity is related to STAT1α, STAT4, STAT5α, and STAT5β. TH9 immunity is related to STAT6, STAT5α, STAT5β, and PU.1. TH17 immunity is related to STAT3α, STAT5α, STAT5β, and RORG. TH3 immunity is related to STAT1α, STAT1β, STAT2, STAT3β, STAT5α, STAT5β, and ISGF. This categorization provides a complete framework of immunological pathways against four types of parasitic infections. This framework as well as relevant JAK/STAT signaling can provide useful knowledge to control allergic hypersensitivities and parasitic infections via development of vaccines or drugs in the near future.

scholarly journals A framework of host immune responses against four types of parasitic infections

2020 ◽  
Author(s):  
Wan-Chung Hu
Keyword(s):  
T Cells ◽  
B Cells ◽  
Mast Cells ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Immunoglobulin E ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Parasitic Infections ◽  
Host Immune Responses

Human host immune responses to parasitic infections are complex. They can be categorized into four immunological pathways against four types of parasitic infections. For intracellular protozoa, the eradicable host immunological pathway is TH1 immunity involving macrophages, interferon gamma (IFNg) CD4 T cells, innate lymphoid cells 1 (ILC1), CD8 T cells, invariant natural killer T cells 1 (iNKT1) cells, and immunoglobulin G3 (IgG3) B cells. For free-living extracellular protozoa, the eradicable host immunological pathway is TH22 immunity involving neutrophils, interleukin (IL)-22/IL-17 CD4 T cells, innate lymphoid cells 3 (ILC3), iNKT17 cells, and IgG2 B cells. For endoparasites (helminths), the eradicable host immunological pathway is TH2a immunity with inflammatory eosinophils (iEOS), IL-5/IL-4 CD4 T cells, IL-25 inducing inflammatory innate lymphoid cells 2 (iILC2), mast cells-tryptase (MCt), iNKT2 cells, and IgG4 B cells. For ectoparasites (parasitic insects and arachnids), the eradicable host immunological pathway is TH2b immunity with inflammatory basophils, mast cells-tryptase/chymase (MCtc), IL-3/IL-4 CD4 T cells, IL-33 inducing nature innate lymphoid cells 2 (nILC2), iNKT2 cells, and immunoglobulin E (IgE) B cells. The tolerable host immunity against ectoparasites and endoparasites is TH9 immunity with regulatory eosinophils, regulatory basophils, IL-9 mast cells (MMC9), thymic stromal lymphopoietin inducing innate lymphoid cells 2, IL-9 CD4 T cells, iNKT2 cells, and IgA2 B cells. This categorization provides a complete framework of immunological pathways against four types of parasitic infections.

scholarly journals Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells

Science ◽  
2015 ◽  
Vol 348 (6238) ◽  
pp. 1031-1035 ◽  
Author(s):  
M. R. Hepworth ◽  
T. C. Fung ◽  
S. H. Masur ◽  
J. R. Kelsen ◽  
F. M. McConnell ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Commensal Bacteria ◽  
Group 3 ◽  
Selection Of

scholarly journals Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

2020 ◽  
Author(s):  
Xiaoyi Li ◽  
Qifan Zhang ◽  
Wanyue Zhang ◽  
Guofu Ye ◽  
Yanchen Ma ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Hepatitis B ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Hbv Infection ◽  
Follicular Dendritic Cells ◽  
Chronic Hbv Infection ◽  
Chronic Hbv

Abstract Background: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4 + T cells and CD19 + B cells.Results: We found that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared with that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, a positive correlation between the frequency of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5) + CD4 + T cells and CXCR5 + CD8 + T cells was also observed. Notably, in vitro experiments demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4 + T cells and promoted the proliferation of autologous intrasplenic CD19 + B cells. Conclusions: Expanded FDCs in patients with chronic HBV infection may favor the host immune responses against HBV. The identification of this unique population may contribute to a better understanding of the immune regulatory mechanisms and provide a potential immunotherapeutic target in chronic HBV infection.

scholarly journals 2019 ATVB Plenary Lecture

2020 ◽  
Vol 40 (4) ◽  
pp. 853-864 ◽  
Author(s):  
Tian X. Zhao ◽  
Stephen A. Newland ◽  
Ziad Mallat
Keyword(s):  
Cardiovascular Disease ◽  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Interleukin 2 ◽  
Cell Types ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Myocardial Repair

Regulatory T cells and type-2 innate lymphoid cells represent 2 subsets of immune cells, which have been shown in preclinical models to be important in atherosclerosis and myocardial repair. Regulatory T cells play a crucial role in immune homeostasis and tolerance via their interactions with effector T cells, dendritic cells, and monocytes/macrophages. They also utilize and secrete inhibitory cytokines, including interleukin 10 and transforming growth factor β, to regulate or suppress pathogenic immune responses. Type-2 innate lymphoid cells have an important role in type-2 immune responses and tissue repair through secreting interleukins 5 and 13, as well as a variety of biological mediators and growth factors. Intriguingly, interleukin-2 has emerged as a common cytokine, which can be harnessed to upregulate both cell types, and also has important translational consequences as clinical trials are ongoing for its use in cardiovascular disease. Here, we briefly review the biology of these regulatory immune cell types, discuss the preclinical and clinical evidence for their functions in cardiovascular disease, examine the prospects for clinical translation and current ongoing trials, and finally, postulate how overlap in the mechanisms of upregulation may be leveraged in future treatments for patients.

scholarly journals Conventional CD4+ T cells regulate IL-22-producing intestinal innate lymphoid cells

2014 ◽  
Vol 7 (5) ◽  
pp. 1045-1057 ◽  
Author(s):  
L L Korn ◽  
H L Thomas ◽  
H G Hubbeling ◽  
S P Spencer ◽  
R Sinha ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells

scholarly journals The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice.

1992 ◽  
Vol 176 (4) ◽  
pp. 1091-1098 ◽  
Author(s):  
R A Seder ◽  
W E Paul ◽  
M M Davis ◽  
B Fazekas de St Groth
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
Inhibitory Effect ◽  
Interleukin 4 ◽  
Ifn Gamma

To study the factors that determine whether CD4+ T cells produce interleukin 4 (IL-4) or interferon gamma (IFN-gamma) upon stimulation we used a system allowing naive T cells to be primed in vitro by specific antigen. Dense CD4+ T cells were purified from mice that expressed transgenes encoding a T cell receptor specific for pigeon cytochrome C peptide 88-104 in association with I-Ek. These T cells produced very limited amounts of IL-4 and IFN-gamma upon immediate challenge with 88-104 and antigen-presenting cells (APC). However, after an initial "priming" culture in which they were incubated for 4 d in the presence of 88-104, APC, and 1,000 U/ml IL-4, the T cells acquired the capacity to produce substantial amounts of IL-4 upon rechallenge but made very little IFN-gamma. Cells primed in the absence of IL-4 produced IFN-gamma upon rechallenge but virtually no IL-4. The inhibitory effect of IL-4 on IFN-gamma production did not appear to be mediated by the induction of IL-10 production since IL-10 addition to initial cultures did not suppress priming for IFN-gamma production, nor did anti-IL-10 block the inhibitory effect of IL-4. IFN-gamma itself did not increase priming for IFN-gamma production, nor did anti-IFN-gamma reduce such priming. IFN-gamma did, however, diminish priming for IL-4 production when limiting amounts of IL-4 (100 U/ml) were used in the initial culture. The dominant effect of IL-4 in determining the lymphokine-producing phenotype of primed cells was observed with dendritic cells (DC), activated B cells, and I-Ek-transfected fibroblasts as APC. However, the different APC did vary in their potency, with DC being superior to activated B cells, which were superior to transfected fibroblasts.

Cell-cell cooperation at the T helper cell/mast cell immunological synapse

Blood ◽  
2009 ◽  
Vol 114 (24) ◽  
pp. 4979-4988 ◽  
Author(s):  
Nicolas Gaudenzio ◽  
Nicolas Espagnolle ◽  
Lennart T. Mars ◽  
Roland Liblau ◽  
Salvatore Valitutti ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cells ◽  
Cd4 T Cells ◽  
Laser Scanning ◽  
Class Ii ◽  
Interferon Γ ◽  
Laser Scanning Microscopy ◽  
Interleukin 4 ◽  
Confocal Laser ◽  
Peritoneal Mast Cells

Abstract It has been suggested that mast cells might serve, under certain circumstances, as antigen-presenting cells (APCs) for T cells. However, whether cognate interactions between mast cells and class II–restricted CD4+ T cells actually occur is still an open question. We addressed this question by using peritoneal cell–derived mast cells (PCMCs) and freshly isolated peritoneal mast cells as APC models. Our results show that in vitro treatment of PCMCs with interferon-γ and interleukin-4 induced surface expression of mature major histocompatibility complex class II molecules and CD86. When interferon-γ/interleukin-4–primed PCMCs were used as APCs for CD4+ T cells, they induced activation of effector T cells but not of their naive counterparts as evidenced by CD69 up-regulation, proliferation, and cytokine production. Confocal laser scanning microscopy showed that CD4+ T cells formed immunological synapses and polarized their secretory machinery toward both antigen-loaded PCMCs and freshly isolated peritoneal mast cells. Finally, on cognate interaction with CD4+ T cells, mast cells lowered their threshold of activation via FcϵRI. Our results show that mast cells can establish cognate interactions with class II–restricted helper T cells, implying that they can actually serve as resident APCs in inflamed tissues.

Incompletely Activated CD4+ T Cells Induce Granzyme B+ Regulatory B Cells In An Interleukin 21-Dependent Manner

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3905-3905
Author(s):  
Bernd Jahrsdoerfer ◽  
Karen Dahlke ◽  
Magdalena Hagn ◽  
Kai Sontheimer ◽  
Thamara Beyer ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Granzyme B ◽  
T Cell Proliferation ◽  
Dependent Manner ◽  
Cellular Immune

Abstract Abstract 3905 Immune regulation is central for the development of an efficient cellular immune response. Both Treg cells and plasmacytoid DC can suppress T cell proliferation in a granzyme B (GzmB)-dependent and perforin-independent manner. In the present study we found that, depending on stimulation with interleukin (IL-) 21, B cells (BC) can also express GzmB and effectively suppress T cell proliferation. GzmB expression in BC is enhanced by BC receptor engagement, and is suppressed by CD40 ligation. Since CD4+ T cells are a main source of IL-21, we tested whether they can induce GzmB in BC. We found that incompletely activated CD4+ T cells, but not fully activated T cells induce GzmB in co-cultured BC. Using confocal microscopy, we showed that BC-derived GzmB is enzymatically active and that GzmB+ BC transfer GzmB to CD4+ T cells. Furthermore, GzmB+ BC decreased CD4+ T cell expression of the TCR-zeta chain, a GzmB target, which is required for T cell proliferation. Our results suggest BC may regulate cellular adaptive immune responses by Treg cell-like mechanisms. Inhibition of BC-derived GzmB may represent a novel strategy to induce more effective and comprehensive cellular immune responses. Disclosures: No relevant conflicts of interest to declare.

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