Targeting Autophagy in Innate Immune Cells: Angel or Demon During Infection and Vaccination?

Tao, Sha; Drexler, Ingo

doi:10.3389/fimmu.2020.00460

Cited by 27 publications

(38 citation statements)

References 109 publications

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“…Altered endosome motility would play an important but complex role in infection and the innate immune response, and might either promote or hinder the battle between SARS-CoV-2 and its human host 22,52 . Coronaviruses including SARS-CoV-2 mainly enter host cells via binding to the ACE2 receptor followed by endocytosis 7,53 .…”

Section: Discussionmentioning

confidence: 99%

African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors that are associated with immunologic and infectious functions and environmental exposures

Singh¹,

Hernandez²,

Aronow³

et al. 2020

Preprint

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The COVID-19 pandemic has affected African American populations disproportionately with respect to prevalence, morbidity, and mortality. Because gene expression profiles represent combined genetic, socioenvironmental, and physiological effects, and could provide therapeutic biomarkers and environmental mitigation strategies, we undertook a large-scale assessment of differential gene expression between African Americans and European Americans. To do this, we mined RNA-Seq datasets from normal and diseased (tumor) conditions whose metadata could be used to evaluate differential patterns. We observed widespread differential expression of genes implicated in COVID-19 and integral to epithelial boundary function, inflammation, infection, and reactive oxygen stress. Notably, expression of the little-studied F8A2 gene is up to 40-fold greater in African Americans. F8A2, like F8A1, encodes HAP40 protein, which mediates early endosome movement. African American gene expression signatures reveal increased number or activity of esophageal glandular cells and lung ACE2-positive basal keratinocytes. These findings have potential to establish prognostic signatures, refine approaches to minimizing risk of severe infection, and improve precision treatment of COVID-19.

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Section: Discussionmentioning

confidence: 99%

African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors that are associated with immunologic and infectious functions and environmental exposures

Singh¹,

Hernandez²,

Aronow³

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Endosome motility and development play an important but complex role in the innate immune response, which can either promote or hinder the battle between SARS-CoV-2 and its human host 51,54,73,74 . Coronaviruses including SARS-CoV-2 mainly enter host cells via binding to the ACE2 receptor followed by endocytosis 20,29,51 .…”

Section: Discussionmentioning

confidence: 99%

“…This regulated development enables diverse fates. For example, in the context of SARS-CoV-2, endosomes might release viral RNA or particles; they might merge with lysosomes and digest their viral cargo; or might fuse with autophagosomes (autophagy) and subsequently with lysosomes that digest the cargo 51,54,73,74 . SARS-CoV-2 might reprogram cellular metabolism, suppressing autophagy and promoting viral replication, 75 .…”

Section: Discussionmentioning

confidence: 99%

“…SARS-Cov-2 and other coronaviruses mainly enter host cells via binding to the ACE2 receptor followed by endocytosis 20,29,51 . The nascent early endosomes are moved along the microtubule cytoskeleton, fusing with other vesicles; varied molecules can be incorporated into the membrane or the interior 51,[79][80][81] . This regulated development enables diverse fates.…”

Section: F8as Endocytosis and Autophagymentioning

confidence: 99%

“…Endosome motility and development thus plays an important but complex role in the innate immune response that can either promote or hinder the battle between SARS-CoV-2 and its human host 51,[79][80][81] .…”

Section: /14mentioning

confidence: 99%

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Differential expression of COVID-19-related genes in European Americans and African Americans

Singh

Wurtele

2020

Preprint

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The Coronavirus disease 2019 (COVID-19) pandemic has affected African American populations disproportionately in regards to both morbidity and mortality. A multitude of factors likely account for this discrepancy. Gene expression represents the interaction of genetics and environment. To elucidate whether levels of expression of genes implicated in COVID-19 vary in African Americans as compared to European Americans, we re-mine The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) RNA-Seq data. Multiple genes integral to infection, inflammation and immunity are differentially regulated across the two populations. Most notably, F8A2 and F8A3, which encode the HAP40 protein that mediates early endosome movement in Huntington’s Disease, are more highly expressed by up to 24-fold in African Americans. Such differences in gene expression can establish prognostic signatures and have critical implications for precision treatment of diseases such as COVID-19. We advocate routine inclusion of information such as postal code, education level, and profession (as a proxies for socioeconomic condition) and race in the metadata about each individual sampled for sequencing studies. This relatively simple change would enable large-scale data-driven approaches to dissect relationships among race, socio-economic factors, and disease.

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Mouse dendritic cells in the steady state: Hypoxia, autophagy, and stem cell factor

Seijas

Simonetti

Filippi

et al. 2022

Cell Biochemistry & Function

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Dendritic cells (DCs) are innate immune cells with a central role in immunity and tolerance. Under steady‐state, DCs are scattered in tissues as resting cells. Upon infection or injury, DCs get activated and acquire the full capacity to prime antigen‐specific CD4+ and CD8+ T cells, thus bridging innate and adaptive immunity. By secreting different sets of cytokines and chemokines, DCs orchestrate diverse types of immune responses, from a classical proinflammatory to an alternative pro‐repair one. DCs are highly heterogeneous, and physiological differences in tissue microenvironments greatly contribute to variations in DC phenotype. Oxygen tension is normally low in some lymphoid areas, including bone marrow (BM) hematopoietic niches; nevertheless, the possible impact of tissue hypoxia on DC physiology has been poorly investigated. We assessed whether DCs are hypoxic in BM and spleen, by staining for hypoxia‐inducible‐factor‐1α subunit (HIF‐1α), the master regulator of hypoxia‐induced response, and pimonidazole (PIM), a hypoxic marker, and by flow cytometric analysis. Indeed, we observed that mouse DCs have a hypoxic phenotype in spleen and BM, and showed some remarkable differences between DC subsets. Notably, DCs expressing membrane c‐kit, the receptor for stem cell factor (SCF), had a higher PIM median fluorescence intensity (MFI) than c‐kit− DCs, both in the spleen and in the BM. To determine whether SCF (a.k.a. kit ligand) has a role in DC hypoxia, we evaluated molecular pathways activated by SCF in c‐kit+ BM‐derived DCs cultured in hypoxic conditions. Gene expression microarrays and gene set enrichment analysis supported the hypothesis that SCF had an impact on hypoxia response and inhibited autophagy‐related gene sets. Our results suggest that hypoxic response and autophagy, and their modulation by SCF, can play a role in DC homeostasis at the steady state, in agreement with our previous findings on SCF's role in DC survival.

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Targeting Autophagy in Innate Immune Cells: Angel or Demon During Infection and Vaccination?

Cited by 27 publications

References 109 publications

African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors that are associated with immunologic and infectious functions and environmental exposures

African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors that are associated with immunologic and infectious functions and environmental exposures

Differential expression of COVID-19-related genes in European Americans and African Americans

Mouse dendritic cells in the steady state: Hypoxia, autophagy, and stem cell factor

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