Myeloid-like γδ T cell subset in the immune response to an experimental Rift Valley fever vaccine in sheep

Lebedev, Maxim; Faburay, Bonto; Richt, Jüergen A.; Young, Alan J.

doi:10.1016/j.vetimm.2021.110184

Cited by 4 publications

(6 citation statements)

References 51 publications

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“…The expression of both Gr-1 and CD11b on the g/d T cells in this study is consistent with their IFNg production. Gr-1 has been used as a marker of IFNg-producing rather than IL-17producing g/d T cells in the setting of bacterial pneumonia (55), and CD11b+ g/d T cells are reported to produce IFNg and to present exogenous antigens (56). Together the phenotype of these g/d T cells suggests they are responding to and exacerbating fetal inflammation in this model.…”

Section: Discussionmentioning

confidence: 86%

IFNγ-Producing γ/δ T Cells Accumulate in the Fetal Brain Following Intrauterine Inflammation

et al. 2021

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Intrauterine inflammation impacts prenatal neurodevelopment and is linked to adverse neurobehavioral outcomes ranging from cerebral palsy to autism spectrum disorder. However, the mechanism by which a prenatal exposure to intrauterine inflammation contributes to life-long neurobehavioral consequences is unknown. To address this gap in knowledge, this study investigates how inflammation transverses across multiple anatomic compartments from the maternal reproductive tract to the fetal brain and what specific cell types in the fetal brain may cause long-term neuronal injury. Utilizing a well-established mouse model, we found that mid-gestation intrauterine inflammation resulted in a lasting neutrophil influx to the decidua in the absence of maternal systemic inflammation. Fetal immunologic changes were observed at 72-hours post-intrauterine inflammation, including elevated neutrophils and macrophages in the fetal liver, and increased granulocytes and activated microglia in the fetal brain. Through unbiased clustering, a population of Gr-1+ γ/δ T cells was identified as the earliest immune cell shift in the fetal brain of fetuses exposed to intrauterine inflammation and determined to be producing high levels of IFNγ when compared to γ/δ T cells in other compartments. In a case-control study of term infants, IFNγ was found to be elevated in the cord blood of term infants exposed to intrauterine inflammation compared to those without this exposure. Collectively, these data identify a novel cellular immune mechanism for fetal brain injury in the setting of intrauterine inflammation.

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Section: Discussionmentioning

confidence: 86%

IFNγ-Producing γ/δ T Cells Accumulate in the Fetal Brain Following Intrauterine Inflammation

et al. 2021

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“…While this population presents some similarity with innate-like T-cells (Molgora and Colonna, 2022), which harbor cytotoxic signatures and whose roles in cancer have been investigated, MTC appear to be unique given their combination of lymphoid, myeloid and mesenchymal markers and their short-lived, apoptotic nature suggested by their complete absence at 12 dpi. MTC also share transcriptomic similarities with γδ T-cell subsets previously described as bearing myeloid and cytotoxic functions (Lebedev et al, 2021;Muto et al, 2015). However, their expression of conventional macrophage makers emphasizes their uniqueness.…”

Section: Discussionmentioning

confidence: 86%

A Novel Human Extravascular Monocyte Subset with Antiviral Functions Is Crucial for Resolving Lung Tissue Infection

Kenney,

O’Connell,

Tseng

et al. 2024

Preprint

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The lung-resident immune mechanisms driving resolution of SARS-CoV-2 infection in humans remain elusive. Using mice co-engrafted with a genetically matched human immune system and fetal lung xenograft (fLX), we mapped the immunological events defining resolution of SARS-CoV-2 infection in human lung tissues. Viral infection is rapidly cleared from fLX following a peak of viral replication. Acute replication results in the emergence of cell subsets enriched in viral RNA, including extravascular inflammatory monocytes (iMO) and macrophage-like T-cells, which dissipate upon infection resolution. iMO display robust antiviral responses, are transcriptomically unique among myeloid lineages, and their emergence associates with the recruitment of circulating CD4+ monocytes. Consistently, mice depleted for human CD4+ cells but not CD3+ T-cells failed to robustly clear infectious viruses and displayed signatures of chronic infection. Our findings uncover the transient differentiation of extravascular iMO from CD4+ monocytes as a major hallmark of SARS-CoV-2 infection resolution and open avenues for unravelling viral and host adaptations defining persistently active SARS-CoV-2 infection.

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“…Compared to unconventional γδT cells, the role for conventional αβT cells in the host responses to vector-borne pathogens has been more extensively and comprehensively studied, for instance Chikungunya virus ( 81 – 83 ), Rift Valley Fever virus ( 28 ), Yellow fever virus ( 84 , 85 ), Zika virus ( 86 , 87 ), West Nile virus ( 88 ), Malaria ( 89 , 90 ), Borrelia burgdorferi ( 91 ), and Leishmaniasis ( 73 , 92 ). However, as above-reviewed, our understanding of the role for γδT cells in these processes has been preliminary and incomplete.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to other ruminants, the sheep’s γδT cells account for a major population of its peripheral blood mononuclear cells. When recombinant Rift Valley Fever vaccine has been injected into the sheep, the percentage of CD11b + γδT in its peripheral blood mononuclear cells can be significantly increased, suggesting that these cells may be critical for the host responses in respond to the virus infection ( 28 ).…”

Section: Immune Responses Of the Host γδT Cells To Mosquito-borne Pat...mentioning

confidence: 99%

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A diversified role for γδT cells in vector-borne diseases

Chen

Yang

2022

Front. Immunol.

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Vector-borne diseases have high morbidity and mortality and are major health threats worldwide. γδT cells represent a small but essential subpopulation of T cells. They reside in most human tissues and exert important functions in both natural and adaptive immune responses. Emerging evidence have shown that the activation and expansion of γδT cells invoked by pathogens play a diversified role in the regulation of host-pathogen interactions and disease progression. A better understanding of such a role for γδT cells may contribute significantly to developing novel preventative and therapeutic strategies. Herein, we summarize recent exciting findings in the field, with a focus on the role of γδT cells in the infection of vector-borne pathogens.

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Myeloid-like γδ T cell subset in the immune response to an experimental Rift Valley fever vaccine in sheep

Cited by 4 publications

References 51 publications

IFNγ-Producing γ/δ T Cells Accumulate in the Fetal Brain Following Intrauterine Inflammation

IFNγ-Producing γ/δ T Cells Accumulate in the Fetal Brain Following Intrauterine Inflammation

A Novel Human Extravascular Monocyte Subset with Antiviral Functions Is Crucial for Resolving Lung Tissue Infection

A diversified role for γδT cells in vector-borne diseases

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