NOTCH1 and DLL4 are involved in the human tuberculosis progression and immune response activation
Copyright © 2020 Elsevier Ltd. All rights reserved..
Tuberculosis (TB) is the leading cause of mortality among infectious diseases worldwide. The study of molecular targets for therapy and diagnosis suggested that Notch signaling is an important pathway for the maintenance of the immune response during Mycobacterium tuberculosis (Mtb) infection. We evaluated the participation of the Notch pathway in the modulation of immune response during Mtb infection, and observed that patients with active TB had increased DLL4 expression in intermediate and non-classic monocytes. Further, patients with moderate and advanced lung injury have higher Notch1 expression in CD4+ T cells when compared to patients with a minimal lung injury. When we considered the severity of disease in active TB patients, the expression of the DLL4 in intermediate monocytes and the expression of Notch1 in CD4+ T cells are positively correlated with the degree of lung injury. In vitro, PBMCs treated with the Notch pharmacological inhibitor reduced the production of IL-17A and IL-2, whereas anti-hDLL4 treatment promoted a significant increase in TNF-α and phagocytosis. We suggest that Notch1 and DLL4 are associated with immune response activation in human tuberculosis, and can be a novel target to be exploited in the future in the searching of biomarkers.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:124 |
|---|---|
| Enthalten in: |
Tuberculosis (Edinburgh, Scotland) - 124(2020) vom: 15. Sept., Seite 101980 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Castro, Ricardo C [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 02.09.2021 Date Revised 09.11.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.tube.2020.101980 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM31375666X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM31375666X | ||
| 003 | DE-627 | ||
| 005 | 20231225151245.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.tube.2020.101980 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1045.xml |
| 035 | |a (DE-627)NLM31375666X | ||
| 035 | |a (NLM)32801053 | ||
| 035 | |a (PII)S1472-9792(20)30147-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Castro, Ricardo C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a NOTCH1 and DLL4 are involved in the human tuberculosis progression and immune response activation |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.09.2021 | ||
| 500 | |a Date Revised 09.11.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Tuberculosis (TB) is the leading cause of mortality among infectious diseases worldwide. The study of molecular targets for therapy and diagnosis suggested that Notch signaling is an important pathway for the maintenance of the immune response during Mycobacterium tuberculosis (Mtb) infection. We evaluated the participation of the Notch pathway in the modulation of immune response during Mtb infection, and observed that patients with active TB had increased DLL4 expression in intermediate and non-classic monocytes. Further, patients with moderate and advanced lung injury have higher Notch1 expression in CD4+ T cells when compared to patients with a minimal lung injury. When we considered the severity of disease in active TB patients, the expression of the DLL4 in intermediate monocytes and the expression of Notch1 in CD4+ T cells are positively correlated with the degree of lung injury. In vitro, PBMCs treated with the Notch pharmacological inhibitor reduced the production of IL-17A and IL-2, whereas anti-hDLL4 treatment promoted a significant increase in TNF-α and phagocytosis. We suggest that Notch1 and DLL4 are associated with immune response activation in human tuberculosis, and can be a novel target to be exploited in the future in the searching of biomarkers | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Immune response | |
| 650 | 4 | |a Mycobacterium tuberculosis | |
| 650 | 4 | |a Notch signaling | |
| 650 | 4 | |a Progression biomarker | |
| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Calcium-Binding Proteins |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a DLL4 protein, human |2 NLM | |
| 650 | 7 | |a NOTCH1 protein, human |2 NLM | |
| 650 | 7 | |a Receptor, Notch1 |2 NLM | |
| 700 | 1 | |a Zambuzi, Fabiana A |e verfasserin |4 aut | |
| 700 | 1 | |a Fontanari, Caroline |e verfasserin |4 aut | |
| 700 | 1 | |a de Morais, Fabiana R |e verfasserin |4 aut | |
| 700 | 1 | |a Bollela, Valdes R |e verfasserin |4 aut | |
| 700 | 1 | |a Kunkel, Steven L |e verfasserin |4 aut | |
| 700 | 1 | |a Schaller, Matthew A |e verfasserin |4 aut | |
| 700 | 1 | |a Frantz, Fabiani G |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Tuberculosis (Edinburgh, Scotland) |d 2001 |g 124(2020) vom: 15. Sept., Seite 101980 |w (DE-627)NLM113651538 |x 1873-281X |7 nnns |
| 773 | 1 | 8 | |g volume:124 |g year:2020 |g day:15 |g month:09 |g pages:101980 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.tube.2020.101980 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 124 |j 2020 |b 15 |c 09 |h 101980 | ||