scholarly journals CD30 Is Required for Activation of a Unique Subset of Interleukin-17A-Producing γδ T Cells in Innate Immunity against Mycobacterium bovis Bacillus Calmette-Guérin Infection

2013 ◽  
Vol 81 (10) ◽  
pp. 3923-3934 ◽  
Author(s):  
Ying Guo ◽  
Xun Sun ◽  
Kensuke Shibata ◽  
Hisakata Yamada ◽  
Hiromi Muta ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Bovis ◽  
Early Stage ◽  
Γδ T Cells ◽  
Bacillus Calmette Guerin ◽  
Content Type ◽  
Interleukin 17A ◽  
Soluble Cd30 ◽  
Infection Inhibition

ABSTRACTInterleukin-17A (IL-17A)-producing γδ T cells are known to be activated followingMycobacterium bovisbacillus Calmette-Guérin (BCG) infection. Here, we show that CD30, a member of the tumor necrosis factor (TNF) receptor superfamily, is important for activation of IL-17A-producing γδ T cells after BCG infection. Vγ1−Vγ4−γδ T cells preferentially expressing Vγ6/Vδ1 genes were identified as the major source of IL-17A in the peritoneal cavity during the early stage of BCG infection. The number of IL-17A-producing Vγ1−Vγ4−γδ T cells bearing Vγ6 increased in peritoneal exudate cells (PEC) of wild-type (WT) mice but not in those of CD30 knockout (KO) mice in response to BCG infection. Consistently, CD30 ligand (CD30L) or CD30 expression, predominantly by Vγ1−Vγ4−γδ T cells, was rapidly upregulated after BCG infection. Inhibition of CD30L/CD30 signaling byin vivoadministration of a soluble CD30 and immunoglobulin fusion protein (CD30-Ig) severely impaired activation of IL-17A-producing Vγ1−Vγ4−γδ T cells in WT mice, while stimulating CD30L/CD30 signaling byin vivoadministration of agonistic anti-CD30 monoclonal antibody (MAb) restored IL-17A production by Vγ1−Vγ4−γδ T cells in CD30L KO mice after BCG infection. These results suggest that CD30 signaling plays an important role in the activation of IL-17A-producing Vγ1−Vγ4−γδ T cells bearing Vγ6 at an early stage of BCG infection.

scholarly journals Protective Role of Naturally Occurring Interleukin-17A-Producing γδ T Cells in the Lung at the Early Stage of Systemic Candidiasis in Mice

2011 ◽  
Vol 79 (11) ◽  
pp. 4503-4510 ◽  
Author(s):  
Takashi Dejima ◽  
Kensuke Shibata ◽  
Hisakata Yamada ◽  
Hiromitsu Hara ◽  
Yoichiro Iwakura ◽  
...  
Keyword(s):  
T Cells ◽  
Early Stage ◽  
Γδ T Cells ◽  
Protective Role ◽  
Dependent Manner ◽  
Peripheral Tissues ◽  
Content Type ◽  
Naturally Occurring ◽  
Interleukin 17A

ABSTRACTInterleukin-17A (IL-17A)-producing γδ T cells differentiate in the fetal thymus and reside in the peripheral tissues, such as the lungs of naïve adult mice. We show here that naturally occurring γδ T cells play a protective role in the lung at a very early stage after systemic infection withCandida albicans.Selective depletion of neutrophils byin vivoadministration of anti-Ly6G monoclonal antibody (MAb) impaired fungal clearance more prominently in the lung than in the kidney 24 h after intravenous infection withC. albicans.Rapid and transient production of IL-23 was detected in the lung at 12 h, preceding IL-17A production and the influx of neutrophils, which reached a peak at 24 h after infection. IL-17A knockout (KO) mice showed reduced infiltration of neutrophils concurrently with impaired fungal clearance in the lung after infection. The major source of IL-17A was the γδ T cell population in the lung, and Cδ KO mice showed little IL-17A production and reduced neutrophil infiltration after infection. Early IL-23 production in a TLR2/MyD88-dependent manner and IL-23-triggered tyrosine kinase 2 (Tyk2) signaling were essential for IL-17A production by γδ T cells. Thus, our study demonstrated a novel role of naturally occurring IL-17A-producing γδ T cells in the first line of host defense againstC. albicansinfection.

scholarly journals Reduced Immune Response to Borrelia burgdorferi in the Absence of γδ T Cells

2011 ◽  
Vol 79 (10) ◽  
pp. 3940-3946 ◽  
Author(s):  
Cuixia Shi ◽  
Bikash Sahay ◽  
Jennifer Q. Russell ◽  
Karen A. Fortner ◽  
Nicholas Hardin ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Borrelia Burgdorferi ◽  
Adaptive Immune Response ◽  
Γδ T Cells ◽  
Content Type ◽  
Adaptive Immune ◽  
Cytokines And Chemokines

ABSTRACTLittle is known regarding the function of γδ T cells, although they accumulate at sites of inflammation in infections and autoimmune disorders. We previously observed that γδ T cellsin vitroare activated byBorrelia burgdorferiin a TLR2-dependent manner. We now observe that the activated γδ T cells can in turn stimulate dendritic cellsin vitroto produce cytokines and chemokines that are important for the adaptive immune response. This suggested thatin vivoγδ T cells may assist in activating the adaptive immune response. We examined this possibilityin vivoand observed that γδ T cells are activated and expand in number duringBorreliainfection, and this was reduced in the absence of TLR2. Furthermore, in the absence of γδ T cells, there was a significantly blunted response of adaptive immunity, as reflected in reduced expansion of T and B cells and reduced serum levels of anti-Borreliaantibodies, cytokines, and chemokines. This paralleled a greaterBorreliaburden in γδ-deficient mice as well as more cardiac inflammation. These findings are consistent with a model of γδ T cells functioning to promote the adaptive immune response during infection.

scholarly journals IL-17 production by γδ T cells is important for the antitumor effect of Mycobacterium bovis bacillus Calmette-Guérin treatment against bladder cancer

2010 ◽  
Vol 41 (1) ◽  
pp. 246-251 ◽  
Author(s):  
Ario Takeuchi ◽  
Takashi Dejima ◽  
Hisakata Yamada ◽  
Kensuke Shibata ◽  
Risa Nakamura ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
Mycobacterium Bovis ◽  
Antitumor Effect ◽  
Γδ T Cells ◽  
Bacillus Calmette Guerin

scholarly journals Interleukin-21 Induces Short-Lived Effector CD8+ T Cells but Does Not Inhibit Their Exhaustion after Mycobacterium bovis BCG Infection in Mice

2018 ◽  
Vol 86 (8) ◽  
Author(s):  
Naoto Noguchi ◽  
Risa Nakamura ◽  
Shinya Hatano ◽  
Hisakata Yamada ◽  
Xun Sun ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Bovis ◽  
Cd8 T Cells ◽  
Absolute Number ◽  
Bacillus Calmette Guerin ◽  
Content Type ◽  
Effector Functions ◽  
Antigen 85B ◽  
Interleukin 21 ◽  
Recombinant Bcg

ABSTRACT Interleukin 21 (IL-21) is a pleiotropic common cytokine receptor γ chain cytokine that promotes the effector functions of NK cells and CD8+ T cells and inhibits CD8+ T cell exhaustion during chronic infection. We found that the absolute number of short-lived effector CD8+ T cells (SLECs) (KLRG1high CD127low) decreased significantly in IL-21 receptor-deficient (IL-21R−/−) mice during Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection. Early effector CD8+ T cells (EECs) (KLRG1low CD127low) were normally generated in IL-21R−/− mice after infection. Exhausted CD8+ T cells (PD-1high KLRG1low) were also normally generated in IL-21R−/− mice after infection. Mixed bone marrow (BM) chimera and transfer experiments showed that IL-21R on CD8+ T cells was essential for the proliferation of EECs, allowing them to differentiate into SLECs after BCG infection. On the other hand, the number of SLECs increased significantly after infection with recombinant BCG (rBCG) that secreted an antigen 85B (Ag85B)–IL-21 fusion protein (rBCG–Ag85B–IL-21), but the number of exhausted CD8+ T cells did not change after rBCG–Ag85B–IL-21 infection. These results suggest that IL-21 signaling drives the differentiation of SLECs from EECs but does not inhibit the exhaustion of CD8+ T cells following BCG infection in mice.

563 IL-17 PRODUCTION BY γδ T CELLS IS IMPORTANT FOR THE ANTITUMOR EFFECT OF MYCOBACTERIUM BOVIS BACILLUS CALMETTE-GUERIN TREATMENT AGAINST BLADDER CANCER

2012 ◽  
Vol 187 (4S) ◽  
Author(s):  
Takashi Dejima ◽  
Ario Takeuchi ◽  
Masatoshi Eto ◽  
Tatsuya Nakatani ◽  
Yasunobu Yoshikai ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
Mycobacterium Bovis ◽  
Antitumor Effect ◽  
Γδ T Cells ◽  
Bacillus Calmette Guerin

Recombinant Mycobacterium bovis bacillus Calmette–Guérin expressing Ag85B-IL-7 fusion protein enhances IL-17A-producing innate γδ T cells

Vaccine ◽  
2016 ◽  
Vol 34 (22) ◽  
pp. 2490-2495 ◽  
Author(s):  
Shinya Hatano ◽  
Toshiki Tamura ◽  
Masayuki Umemura ◽  
Goro Matsuzaki ◽  
Naoya Ohara ◽  
...  
Keyword(s):  
T Cells ◽  
Fusion Protein ◽  
Mycobacterium Bovis ◽  
Γδ T Cells ◽  
Bacillus Calmette Guerin

scholarly journals A Theileria parva Isolate of Low Virulence Infects a Subpopulation of Lymphocytes

2011 ◽  
Vol 80 (3) ◽  
pp. 1267-1273 ◽  
Author(s):  
Heshborne S. Tindih ◽  
Dirk Geysen ◽  
Bruno M. Goddeeris ◽  
Elias Awino ◽  
Dirk A. E. Dobbelaere ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Γδ T Cells ◽  
Target Cells ◽  
Theileria Parva ◽  
Logarithmic Growth Phase ◽  
Peripheral Blood Mononuclear ◽  
Content Type

Theileria parvais a tick-transmitted protozoan parasite that infects and transforms bovine lymphocytes. We have previously shown thatTheileria parvaChitongo is an isolate with a lower virulence than that ofT. parvaMuguga. Lower virulence appeared to be correlated with a delayed onset of the logarithmic growth phase ofT. parvaChitongo-transformed peripheral blood mononuclear cells afterin vitroinfection. In the current study, infection experiments with WC1+γδ T cells revealed that onlyT. parvaMuguga could infect these cells and that no transformed cells could be obtained withT. parvaChitongo sporozoites. Subsequent analysis of the susceptibility of different cell lines and purified populations of lymphocytes to infection and transformation by both isolates showed thatT. parvaMuguga sporozoites could attach to and infect CD4+, CD8+, and WC1+T lymphocytes, butT. parvaChitongo sporozoites were observed to bind only to the CD8+T cell population. Flow cytometry analysis of established, transformed clones confirmed this bias in target cells.T. parvaMuguga-transformed clones consisted of different cell surface phenotypes, suggesting that they were derived from either host CD4+, CD8+, or WC1+T cells. In contrast, allin vitroandin vivoT. parvaChitongo-transformed clones expressed CD8 but not CD4 or WC1, suggesting that theT. parvaChitongo-transformed target cells were exclusively infected CD8+lymphocytes. Thus, a role of cell tropism in virulence is likely. Since the adhesion molecule p67 is 100% identical between the two strains, a second, high-affinity adhesin that determines target cell specificity appears to exist.

scholarly journals IL-21 inhibits IL-17A-producing γδ T-cell response after infection with Bacillus Calmette-Guérin via induction of apoptosis

2016 ◽  
Vol 22 (8) ◽  
pp. 588-597 ◽  
Author(s):  
Yinxia Huang ◽  
Yumiko Matsumura ◽  
Shinya Hatano ◽  
Naoto Noguchi ◽  
Tesshin Murakami ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Early Stage ◽  
Cell Subset ◽  
Γδ T Cells ◽  
T Cell Response ◽  
Bacillus Calmette Guerin ◽  
Γδ T Cell ◽  
Induced Apoptosis

Innate γδ T cells expressing Vγ6 produce IL-17A at an early stage following infection with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In this study, we used IL-21 receptor knockout (IL-21R KO) mice and IL-21-producing recombinant BCG mice (rBCG-Ag85B-IL-21) to examine the role of IL-21 in the regulation of IL-17A-producing innate γδ T-cell response following BCG infection. IL-17A-producing Vγ6+ γδ T cells increased in the peritoneal cavity of IL-21R KO mice more than in wild type mice after BCG infection. In contrast, the number of IL-17A-producing Vγ6+ γδ T cells was significantly lower after inoculation with rBCG-Ag85B-IL-21 compared with control rBCG-Ag85B. Notably, exogenous IL-21 selectively induced apoptosis of IL-17A-producing Vγ6+ γδ T cells via Bim. Thus, these results suggest that IL-21 acts as a potent inhibitor of a IL-17A-producing γδ T-cell subset during BCG infection.

scholarly journals Staphylococcus aureus Fatty Acid Kinase FakA Modulates Pathogenesis during Skin Infection via Proteases

2020 ◽  
Vol 88 (8) ◽  
Author(s):  
Miranda J. Ridder ◽  
Seth M. Daly ◽  
Kathleen D. Triplett ◽  
Nichole A. Seawell ◽  
Pamela R. Hall ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Fatty Acid ◽  
Skin Infection ◽  
Lipid Membrane ◽  
Early Stage ◽  
Content Type ◽  
Interleukin 17A

ABSTRACT Staphylococcus aureus fatty acid kinase FakA is necessary for the incorporation of exogenous fatty acids into the lipid membrane. We previously demonstrated that the inactivation of fakA leads to decreased α-hemolysin (Hla) production but increased expression of the proteases SspAB and aureolysin in vitro, and that the ΔfakA mutant causes larger lesions than the wild type (WT) during murine skin infection. As expected, necrosis is Hla dependent in the presence or absence of FakA, as both hla and hla ΔfakA mutants are unable to cause necrosis of the skin. At day 4 postinfection, while the ΔfakA mutant maintains larger and more necrotic abscesses, bacterial numbers are similar to those of the WT, indicating the enhanced tissue damage of mice infected with the ΔfakA mutant is not due to an increase in bacterial burden. At this early stage of infection, skin infected with the ΔfakA mutant has decreased levels of proinflammatory cytokines, such as interleukin-17A (IL-17A) and IL-1α, compared to those of WT-infected skin. At a later stage of infection (day 7), abscess resolution and bacterial clearance are hindered in ΔfakA mutant-infected mice. The paradoxical findings of decreased Hla in vitro but increased necrosis in vivo led us to investigate the role of the proteases regulated by FakA. Utilizing Δaur and ΔsspAB mutants in both the WT and fakA mutant backgrounds, we found that the absence of these proteases in a fakA mutant reduced dermonecrosis to levels similar to those of the WT strain. These studies suggest that the overproduction of proteases is one factor contributing to the enhanced pathogenesis of the ΔfakA mutant during skin infection.

scholarly journals STAT6 Signaling Attenuates Interleukin-17-Producing γδ T Cells during Acute Klebsiella pneumoniae Infection

2016 ◽  
Vol 84 (5) ◽  
pp. 1548-1555 ◽  
Author(s):  
Melissa H. Bloodworth ◽  
Dawn C. Newcomb ◽  
Daniel E. Dulek ◽  
Matthew T. Stier ◽  
Jacqueline Y. Cephus ◽  
...  
Keyword(s):  
T Cells ◽  
Klebsiella Pneumoniae ◽  
Fungal Pathogens ◽  
Γδ T Cells ◽  
Parasitic Infections ◽  
Interleukin 17 ◽  
Type I ◽  
Content Type ◽  
Antibacterial And Antifungal

γδ T cells are prevalent at mucosal and epithelial surfaces and are a critical first line of defense against bacterial and fungal pathogens. γδ17 cells are a subset of γδ T cells which, in the presence of IL-23 and IL-1β, produce large quantities of interleukin-17A (IL-17A), a cytokine crucial to these cells' antibacterial and antifungal function. STAT6, an important transcription factor in Th2 differentiation and inhibition of Th1 differentiation, is expressed at high levels in the T cells of people with parasitic infections and asthma. Our group and others have shown that STAT6 attenuates IL-17A protein expression by CD4+T cells. By extension, we hypothesized that STAT6 activation also inhibits innate γδ17 cell cytokine secretion. We show here that γδ17 cells expressed the type I IL-4 receptor (IL-4R), and IL-4 increased STAT6 phosphorylation in γδ T cells. IL-4 inhibited γδ17 cell production of IL-17A. IL-4 also decreased γδ17 cell expression of IL-23R as well as Sgk1. To determine whether STAT6 signaling regulates γδ17 cell numbersin vivo, we used a model ofKlebsiella pneumoniaein mice deficient in STAT6. We choseK. pneumoniaefor ourin vivomodel, sinceK. pneumoniaeincreases IL-17A expression and γδ17 numbers.K. pneumoniaeinfection of STAT6 knockout mice resulted in a statistically significant increase in the number of γδ17 cells compared to that of wild-type mice. These studies are the first to demonstrate that γδ17 cells express the type I IL-4R and that STAT6 signaling negatively regulates γδ17 cells, a cell population that plays a front-line role in mucosal immunity.

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