Comparison of host immune responses to LPS in human using an immune profiling panel, in vivo endotoxemia versus ex vivo stimulation

Tawfik, Dina M.; Lankelma, Jacqueline M.; Vachot, Laurence; Cerrato, Elisabeth; Pachot, Alexandre; Wiersinga, W. Joost; Textoris, Julien

doi:10.1038/s41598-020-66695-2

Cited by 24 publications

(23 citation statements)

References 38 publications

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“…Additionally, experimental studies confirmed that alterations in inflammation and kynurenine metabolism can lead to depressive-like behavior. This has been established in animal models [ 37 ] and human volunteers injected with endotoxin to stimulate inflammation [ 38 ]. It is known that interferon- α injections, to treat hepatitis C, lead to depressive symptoms, together with an increase in cytokines and QUIN in the CSF [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Cytokines and tryptophan metabolites can predict depressive symptoms in pregnancy

et al. 2022

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Depression during and after pregnancy affects up to 20% of pregnant women, but the biological underpinnings remain incompletely understood. As pregnancy progresses, the immune system changes to facilitate fetal development, leading to distinct fluctuations in the production of pro-inflammatory factors and neuroactive tryptophan metabolites throughout the peripartum period. Therefore, it is possible that depression in pregnancy could constitute a specific type of inflammation-induced depression. Both inflammatory factors and kynurenine metabolites impact neuroinflammation and glutamatergic neurotransmission and can therefore affect mood and behavior. To determine whether cytokines and kynurenine metabolites can predict the development of depression in pregnancy, we analyzed blood samples and clinical symptoms in 114 women during each trimester and the postpartum. We analyzed plasma IL-1β, IL-2, -6, -8, -10, TNF, kynurenine, tryptophan, serotonin, kynurenic- quinolinic- and picolinic acids and used mixed-effects models to assess the association between biomarkers and depression severity. IL-1β and IL-6 levels associated positively with severity of depressive symptoms across pregnancy and the postpartum, and that the odds of experiencing significant depressive symptoms increased by >30% per median absolute deviation for both IL-1β and IL-6 (both P = 0.01). A combination of cytokines and kynurenine metabolites in the 2nd trimester had a >99% probability of accurately predicting 3rd trimester depression, with an ROC AUC > 0.8. Altogether, our work shows that cytokines and tryptophan metabolites can predict depression during pregnancy and could be useful as clinical markers of risk. Moreover, inflammation and kynurenine pathway enzymes should be considered possible therapeutic targets in peripartum depression.

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Section: Discussionmentioning

confidence: 99%

Cytokines and tryptophan metabolites can predict depressive symptoms in pregnancy

et al. 2022

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“…Additionally, two mitogens were used to evaluate the immunomodulatory effects of the Imuno TF ® : LPS and Con A. Both LPS and Con A are widely used in in vitro and in vivo tests to assess the ability of cells to secrete various types of cytokines [29][30][31].…”

Section: Discussionmentioning

confidence: 99%

Immunoregulatory Effects of Imuno TF® (transfer factors) on Th1/Th2/Th17/Treg Cytokines

2021

JCEI

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Transfer factors are known since 1955 due to their activities on the immune system. Although the reports on the effects on diverse immune mechanisms, their role on Th1, Th2, Th17 and Treg responses was still not described. In this sense, the present work focused on the evaluation of such immune responses. For that, human lymphocytes, and mice thymic, splenic and Peyer’s cells were stimulated with Lipopolysaccharides and Concanavalin A, and then treated with isolated transfer factors (Imuno TF®). The culture medium was harvested and the quantification of Th1 cytokines (IL-2 and IFN-γ), Th2 cytokines (IL-4, IL-5, and IL-13), Th17 cytokine (IL-17), Treg cytokine (IL-35), inflammatory cytokines (IL-6 and TNF-α), and antiinflammatory cytokine (IL-10) was performed, as well as the quantification of mRNA levels. Imuno TF® positively regulated Th1 cytokines, while decreased Th2 cytokines. It also increased levels of mRNA and secretion of the anti-inflammatory cytokine IL-10, whereas it reduced levels of mRNA and the secretion of pro-inflammatory cytokines IL-6 and TNF-α. Finally, it reversed the hypersecretion of IL-17 and did not promote significant changes in IL-35 secretion. This highlights the role of Imuno TF® in the regulation of the immune responses.

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“…LPS, also known as endotoxin, is one of the most potent immunostimulants ( Alexander and Rietschel, 2001 ) and consists of a glycan polymer, oligosaccharide core, and membrane-anchor lipid ( Alexander and Rietschel, 2001 ; Cavaillon, 2018 ). Physiological recognition of the lipid component by the immune system causes pro-inflammatory cytokine activity ( Alexander and Rietschel, 2001 ; Liu et al., 2018 ; Monguió-Tortajada et al., 2018 ; Tawfik et al., 2020 ). Endotoxin is the main driver of pro- and anti-inflammatory cytokine activation in gram-negative bacterial infections ( Feezor et al., 2003 ; Tawfik et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Physiological recognition of the lipid component by the immune system causes pro-inflammatory cytokine activity ( Alexander and Rietschel, 2001 ; Liu et al., 2018 ; Monguió-Tortajada et al., 2018 ; Tawfik et al., 2020 ). Endotoxin is the main driver of pro- and anti-inflammatory cytokine activation in gram-negative bacterial infections ( Feezor et al., 2003 ; Tawfik et al., 2020 ). Endotoxin-induced inflammatory conditions cause similar levels of cytokine expression as those found in septic conditions due to a gram-positive bacteria such as S. aureus , one of the most common bacteria found on the surface of human skin ( Foster, 2004 ; Tawfik et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Endotoxin is the main driver of pro- and anti-inflammatory cytokine activation in gram-negative bacterial infections ( Feezor et al., 2003 ; Tawfik et al., 2020 ). Endotoxin-induced inflammatory conditions cause similar levels of cytokine expression as those found in septic conditions due to a gram-positive bacteria such as S. aureus , one of the most common bacteria found on the surface of human skin ( Foster, 2004 ; Tawfik et al., 2020 ). S. aureus , characterized by its thick, PepG layer and LTA layer, is known to stimulate the immune system through the release of toxins into the bloodstream ( Feezor et al., 2003 ; McNicholas et al., 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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A Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus

Talaei

Garan

Quintela

et al. 2021

Front. Cell. Infect. Microbiol.

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Cell-based mathematical models have previously been developed to simulate the immune system in response to pathogens. Mathematical modeling papers which study the human immune response to pathogens have predicted concentrations of a variety of cells, including activated and resting macrophages, plasma cells, and antibodies. This study aims to create a comprehensive mathematical model that can predict cytokine levels in response to a gram-positive bacterium, S. aureus by coupling previous models. To accomplish this, the cytokines Tumor Necrosis Factor Alpha (TNF-α), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and Interleukin 10 (IL-10) are included to quantify the relationship between cytokine release from macrophages and the concentration of the pathogen, S. aureus, ex vivo. Partial differential equations (PDEs) are used to model cellular response and ordinary differential equations (ODEs) are used to model cytokine response, and interactions between both components produce a more robust and more complete systems-level understanding of immune activation. In the coupled cellular and cytokine model outlined in this paper, a low concentration of S. aureus is used to stimulate the measured cellular response and cytokine expression. Results show that our cellular activation and cytokine expression model characterizing septic conditions can predict ex vivo mechanisms in response to gram-negative and gram-positive bacteria. Our simulations provide new insights into how the human immune system responds to infections from different pathogens. Novel applications of these insights help in the development of more powerful tools and protocols in infection biology.

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Comparison of host immune responses to LPS in human using an immune profiling panel, in vivo endotoxemia versus ex vivo stimulation

Cited by 24 publications

References 38 publications

Cytokines and tryptophan metabolites can predict depressive symptoms in pregnancy

Cytokines and tryptophan metabolites can predict depressive symptoms in pregnancy

Immunoregulatory Effects of Imuno TF® (transfer factors) on Th1/Th2/Th17/Treg Cytokines

A Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus

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