Analysis of Co-inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease
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Analysis of Co-inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease. / Herrmann, Marissa; Schulte, Sophia; Wildner, Nils H.; Wittner, Melanie; Brehm, Thomas Theo; Ramharter, Michael; Woost, Robin; Lohse, Ansgar W.; Jacobs, Thomas; Schulze zur Wiesch, Julian.
in: FRONT IMMUNOL, Jahrgang 11, 1870, 26.08.2020, S. 1870.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Analysis of Co-inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease
AU - Herrmann, Marissa
AU - Schulte, Sophia
AU - Wildner, Nils H.
AU - Wittner, Melanie
AU - Brehm, Thomas Theo
AU - Ramharter, Michael
AU - Woost, Robin
AU - Lohse, Ansgar W.
AU - Jacobs, Thomas
AU - Schulze zur Wiesch, Julian
N1 - Copyright © 2020 Herrmann, Schulte, Wildner, Wittner, Brehm, Ramharter, Woost, Lohse, Jacobs and Schulze zur Wiesch.
PY - 2020/8/26
Y1 - 2020/8/26
N2 - Coronavirus disease 2019 (COVID-19) which is caused by the novel SARS-CoV-2 virus is a severe flu-like illness which is associated with hyperinflammation and immune dysfunction. The virus induces a strong T and B cell response but little is known about the immune pathology of this viral infection. Acute Plasmodium falciparum malaria also causes acute clinical illness and is characterized by hyperinflammation due to the strong production of pro-inflammatory cytokines and a massive activation of T cells. In malaria, T cells express a variety of co-inhibitory receptors which might be a consequence of their activation but also might limit their overwhelming function. Thus, T cells are implicated in protection as well as in pathology. The outcome of malaria is thought to be a consequence of the balance between co-activation and co-inhibition of T cells. Following the hypothesis that T cells in COVID-19 might have a similar, dual function, we comprehensively characterized the differentiation (CCR7, CD45RO) and activation status (HLA-DR, CD38, CD69, CD226), the co-expression of co-inhibitory molecules (PD1, TIM-3, LAG-3, BTLA, TIGIT), as well as the expression pattern of the transcription factors T-bet and eomes of CD8+ and CD4+ T cells of PBMC of n = 20 SARS-CoV-2 patients compared to n = 10 P. falciparum infected patients and n = 13 healthy controls. Overall, acute COVID-19 and malaria infection resulted in a comparably elevated activation and altered differentiation status of the CD8+ and CD4+ T cell populations. T effector cells of COVID-19 and malaria patients showed higher frequencies of the inhibitory receptors T-cell immunoglobulin mucin-3 (TIM-3) and Lymphocyte-activation gene-3 (LAG-3) which was linked to increased activation levels and an upregulation of the transcription factors T-bet and eomes. COVID-19 patients with a more severe disease course showed higher levels of LAG-3 and TIM-3 than patients with a mild disease course. During recovery, a rapid normalization of these inhibitory receptors could be observed. In summary, comparing the expression of different co-inhibitory molecules in CD8+ and CD4+ T cells in COVID-19 vs. malaria, there is a transient increase of the expression of certain inhibitory receptors like LAG-3 and TIM-3 in COVID-19 in the overall context of acute immune activation.
AB - Coronavirus disease 2019 (COVID-19) which is caused by the novel SARS-CoV-2 virus is a severe flu-like illness which is associated with hyperinflammation and immune dysfunction. The virus induces a strong T and B cell response but little is known about the immune pathology of this viral infection. Acute Plasmodium falciparum malaria also causes acute clinical illness and is characterized by hyperinflammation due to the strong production of pro-inflammatory cytokines and a massive activation of T cells. In malaria, T cells express a variety of co-inhibitory receptors which might be a consequence of their activation but also might limit their overwhelming function. Thus, T cells are implicated in protection as well as in pathology. The outcome of malaria is thought to be a consequence of the balance between co-activation and co-inhibition of T cells. Following the hypothesis that T cells in COVID-19 might have a similar, dual function, we comprehensively characterized the differentiation (CCR7, CD45RO) and activation status (HLA-DR, CD38, CD69, CD226), the co-expression of co-inhibitory molecules (PD1, TIM-3, LAG-3, BTLA, TIGIT), as well as the expression pattern of the transcription factors T-bet and eomes of CD8+ and CD4+ T cells of PBMC of n = 20 SARS-CoV-2 patients compared to n = 10 P. falciparum infected patients and n = 13 healthy controls. Overall, acute COVID-19 and malaria infection resulted in a comparably elevated activation and altered differentiation status of the CD8+ and CD4+ T cell populations. T effector cells of COVID-19 and malaria patients showed higher frequencies of the inhibitory receptors T-cell immunoglobulin mucin-3 (TIM-3) and Lymphocyte-activation gene-3 (LAG-3) which was linked to increased activation levels and an upregulation of the transcription factors T-bet and eomes. COVID-19 patients with a more severe disease course showed higher levels of LAG-3 and TIM-3 than patients with a mild disease course. During recovery, a rapid normalization of these inhibitory receptors could be observed. In summary, comparing the expression of different co-inhibitory molecules in CD8+ and CD4+ T cells in COVID-19 vs. malaria, there is a transient increase of the expression of certain inhibitory receptors like LAG-3 and TIM-3 in COVID-19 in the overall context of acute immune activation.
KW - COVID-19
KW - LAG-3
KW - malaria
KW - PD-1
KW - Plasmodium falciparum
KW - SARS-CoV-2
KW - T cells
KW - TIM-3
KW - Betacoronavirus/genetics
KW - Pandemics
KW - Antigens, CD/metabolism
KW - Humans
KW - Middle Aged
KW - Male
KW - CD8-Positive T-Lymphocytes/immunology
KW - Pneumonia, Viral/immunology
KW - Adult
KW - Female
KW - Coronavirus Infections/immunology
KW - Severity of Illness Index
KW - Acute Disease
KW - Malaria, Falciparum/immunology
KW - Cells, Cultured
KW - CD4-Positive T-Lymphocytes/immunology
KW - Lymphocyte Activation/immunology
KW - Aged
KW - Plasmodium falciparum/isolation & purification
KW - Programmed Cell Death 1 Receptor/metabolism
KW - Hepatitis A Virus Cellular Receptor 2/metabolism
KW - Receptors, Antigen, T-Cell/metabolism
KW - Cohort Studies
UR - http://www.scopus.com/inward/record.url?scp=85090822475&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2020.01870
DO - 10.3389/fimmu.2020.01870
M3 - SCORING: Journal article
C2 - 32983106
AN - SCOPUS:85090822475
VL - 11
SP - 1870
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
M1 - 1870
ER -