Protective role of γδ T cells in cigarette smoke and influenza infection

AbstractCOVID-19 is a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first documented in late 2019, but within months, a worldwide pandemic was declared due to the easily transmissible nature of the virus. Research to date on the immune response to SARS-CoV-2 has focused largely on conventional B and T lymphocytes. This review examines the emerging role of unconventional T cell subsets, including γδ T cells, invariant natural killer T (iNKT) cells and mucosal associated invariant T (MAIT) cells in human SARS-CoV-2 infection.Some of these T cell subsets have been shown to play protective roles in anti-viral immunity by suppressing viral replication and opsonising virions of SARS-CoV. Here, we explore whether unconventional T cells play a protective role in SARS-CoV-2 infection as well. Unconventional T cells are already under investigation as cell-based immunotherapies for cancer. We discuss the potential use of these cells as therapeutic agents in the COVID-19 setting. Due to the rapidly evolving situation presented by COVID-19, there is an urgent need to understand the pathogenesis of this disease and the mechanisms underlying its immune response. Through this, we may be able to better help those with severe cases and lower the mortality rate by devising more effective vaccines and novel treatment strategies.

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Protective role of regulatory decidual γδ T cells in pregnancy

Clinical Immunology ◽

10.1016/j.clim.2011.09.004 ◽

2011 ◽

Vol 141 (3) ◽

pp. 236-239 ◽

Cited By ~ 17

Author(s):

Mark A. Exley ◽

Jonathan E. Boyson

Keyword(s):

T Cells ◽

Γδ T Cells ◽

Protective Role ◽

In Pregnancy

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

Infection and Immunity ◽

10.1128/iai.05799-11 ◽

2011 ◽

Vol 79 (11) ◽

pp. 4503-4510 ◽

Cited By ~ 55

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.

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Role of Common γ-Chain Cytokines in Lung Interleukin-22 Regulation after Acute Exposure to Aspergillus fumigatus

Infection and Immunity ◽

10.1128/iai.00157-18 ◽

2018 ◽

Vol 86 (10) ◽

Cited By ~ 3

Author(s):

Kristen M. Reeder ◽

Joseph J. Mackel ◽

Matthew S. Godwin ◽

Chad W. Dunaway ◽

Jonathan P. Blackburn ◽

...

Keyword(s):

T Cells ◽

Aspergillus Fumigatus ◽

Γδ T Cells ◽

Protective Role ◽

Lymphoid Cells ◽

Inkt Cells ◽

Content Type ◽

Interleukin 22 ◽

Cell Sources

ABSTRACT Humans are constantly exposed to the opportunistic mold Aspergillus fumigatus, and disease caused by this pathogen is often determined by the magnitude of local and systemic immune responses. We have previously shown a protective role for interleukin-22 (IL-22) after acute A. fumigatus exposure. Here, employing IL-22Cre R26ReYFP reporter mice, we identified iNKT cells, γδ T cells, and type 3 innate lymphoid cells (ILC3s) as lung cell sources of IL-22 in response to acute A. fumigatus exposure. As these cells often utilize common γ-chain cytokines for their development or maintenance, we determined the role of IL-7, IL-21, and IL-15 in lung IL-22 induction and A. fumigatus lung clearance. We observed that IL-7, IL-21, and IL-15 were essential for, partially required for, or negatively regulated the production of IL-22, respectively. Deficiency in IL-7 and IL-21, but not IL-15R, resulted in impaired fungal clearance. Surprisingly, however, the absence of IL-7, IL-21, or IL-15R signaling had no effect on neutrophil recruitment. The levels of IL-1α, an essential anti-A. fumigatus proinflammatory cytokine, were increased in the absence of IL-7 and IL-15R but decreased in the absence of IL-21. IL-7 was responsible for maintaining lung iNKT cells and γδ T cells, whereas IL-21 was responsible for maintaining lung iNKT cells and ILC3s. In contrast, IL-15R deficiency had no effect on the absolute numbers of any IL-22 cell source, rather resulting in enhanced per cell production of IL-22 by iNKT cells and γδ T cells. Collectively, these results provide insight into how the IL-22 response in the lung is shaped after acute A. fumigatus exposure.

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Gamma Interferon Plays a Crucial Early Antiviral Role in Protection against West Nile Virus Infection

Journal of Virology ◽

10.1128/jvi.00274-06 ◽

2006 ◽

Vol 80 (11) ◽

pp. 5338-5348 ◽

Cited By ~ 139

Author(s):

Bimmi Shrestha ◽

Tian Wang ◽

Melanie A. Samuel ◽

Kevin Whitby ◽

Joe Craft ◽

...

Keyword(s):

T Cells ◽

West Nile Virus ◽

Γδ T Cells ◽

Protective Role ◽

Immunoglobulin M ◽

Cns Infection ◽

Lymphoid Tissues ◽

West Nile ◽

Ifn Γ

ABSTRACT West Nile virus (WNV) causes a severe central nervous system (CNS) infection in humans, primarily in the elderly and immunocompromised. Prior studies have established an essential protective role of several innate immune response elements, including alpha/beta interferon (IFN-α/β), immunoglobulin M, γδ T cells, and complement against WNV infection. In this study, we demonstrate that a lack of IFN-γ production or signaling results in increased vulnerability to lethal WNV infection by a subcutaneous route in mice, with a rise in mortality from 30% (wild-type mice) to 90% (IFN-γ−/− or IFN-γR−/− mice) and a decrease in the average survival time. This survival pattern in IFN-γ−/− and IFN-γR−/− mice correlated with higher viremia and greater viral replication in lymphoid tissues. The increase in peripheral infection led to early CNS seeding since infectious WNV was detected several days earlier in the brains and spinal cords of IFN-γ−/− or IFN-γR−/− mice. Bone marrow reconstitution experiments showed that γδ T cells require IFN-γ to limit dissemination by WNV. Moreover, treatment of primary dendritic cells with IFN-γ reduced WNV production by 130-fold. Collectively, our experiments suggest that the dominant protective role of IFN-γ against WNV is antiviral in nature, occurs in peripheral lymphoid tissues, and prevents viral dissemination to the CNS.

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