Metabolic imbalance of T cells in COVID-19 is hallmarked by basigin and mitigated by dexamethasone

Siska, Peter J.; Decking, Sonja-Maria; Babl, Nathalie; Matos, Carina; Bruß, Christina; Singer, Katrin; Klitzke, Jana; Schön, Marian; Simeth, Jakob; Köstler, Josef; Siegmund, Heiko; Ugele, Ines; Paulus, Michael; Dietl, Alexander; Kolodová, Kristina; Steines, Louisa; Freitag, Katharina; Peuker, Alice; Schönhammer, Gabriele; Raithel, Johanna; Graf, Bernhard M.; Geismann, Florian; Lubnow, Matthias; Mack, Matthias; Hau, Peter; Bohr, Christopher; Burkhardt, Ralph; Gessner, André; Salzberger, Bernd; Wagner, Ralf; Hanses, Frank; Hitzenbichler, Florian; Heudobler, Daniel; Lüke, Florian; Pukrop, Tobias; Herr, Wolfgang; Wolff, Daniel; Spang, Rainer; Poeck, Hendrik; Hoffmann, Petra; Brochhausen, Christoph; Lunz, Dirk; Rehli, Michael; Kreutz, Marina; Renner, Kathrin

doi:10.1172/jci148225

Cited by 28 publications

(33 citation statements)

References 71 publications

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“…The exhaustion in both non-ICU and ICU adult T cells was accompanied by mitochondrial dysfunction and increased expression of OXPHOS genes, particularly in the two ICU adults. Metabolic dysregulation in patients with severe COVID-19 has been previously described (Siska et al, 2021; Thompson et al, 2021). Taken together, these data suggest that SARS-CoV-2-specific T cells from adult were more activated and terminally differentiated than children despite having the same disease severity.…”

Section: Discussionmentioning

confidence: 91%

Section: Similar Local Innate Immune Defense Mechanisms May Operate T...mentioning

confidence: 99%

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Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19

Khoo

Jackson

Phetsouphanh

et al. 2022

Preprint

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Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV-2-specific naive T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. More naive interferon-activated CD4+ T cells were recruited into the memory compartment and recovery was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.

show abstract

Section: Discussionmentioning

confidence: 91%

Section: Similar Local Innate Immune Defense Mechanisms May Operate T...mentioning

confidence: 99%

Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19

Khoo

Jackson

Phetsouphanh

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…This is supported by a study by Siaska et al., where T cell metabolism was differentially affected in mild compared to moderate and severe disease. This was evident by an elevated uptake of fatty acids in T cells from patients with mild or no symptoms, while glucose uptake was similar to that of quiescent T cells from healthy controls ( 153 ). This study also revealed that moderate and severe disease was correlated with increased mitochondrial content, ROS and expression of basigin, which is reported to drive hyperinflammation and bone degradation in rheumatoid arthritis ( 153 , 154 ).…”

Section: T Cell Metabolism In Infectionmentioning

confidence: 91%

T Cell Metabolism in Infection

Wik

Skålhegg

2022

Front. Immunol.

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T lymphocytes (T cells) are divided into two functionally different subgroups the CD4+ T helper cells (Th) and the CD8+ cytotoxic T lymphocytes (CTL). Adequate CD4 and CD8 T cell activation to proliferation, clonal expansion and effector function is crucial for efficient clearance of infection by pathogens. Failure to do so may lead to T cell exhaustion. Upon activation by antigen presenting cells, T cells undergo metabolic reprograming that support effector functions. In this review we will discuss how metabolic reprograming dictates functionality during viral infections using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV) as examples. Moreover, we will briefly discuss T cell metabolic programs during bacterial infections exemplified by Mycobacterium tuberculosis (MT) infection.

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“…T-cell responses are mediated through CD4 + and CD8 + cells and the assessment of T cell responses and humoral immunity in COVID-19 patients have been extensively characterized [ [43] , [44] , [45] ]. In the context of SARS-CoV-2 induced T cell oxidative stress, the mitochondria and the metabolic network participate in ROS generation [ 46 , 47 ]. Specifically, T cell intracellular ROS were accumulated in COVID-19 patients and was associated with mitochondrial mass and architecture [ 47 ].…”

Section: Oxidative Stress From Hematopoietic and Non-hematopoietic Ce...mentioning

confidence: 99%

Redox stress in COVID-19: Implications for hematologic disorders

Yang

2022

Best Practice & Research Clinical Haematology

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Metabolic imbalance of T cells in COVID-19 is hallmarked by basigin and mitigated by dexamethasone

Cited by 28 publications

References 71 publications

Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19

Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19

T Cell Metabolism in Infection

Redox stress in COVID-19: Implications for hematologic disorders

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