Determination of in vitro and in vivo immune response to recombinant cholesterol oxidase from Mycobacterium tuberculosis
Copyright © 2020 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved..
Cholesterol oxidase (ChoD) is an enzyme that is involved but is dispensable in the process of cholesterol degradation by Mycobacterium tuberculosis (Mtb). Interestingly, ChoD is a virulence factor of Mtb, and it strongly modulates the function of human macrophages in vitro, allowing the intracellular survival of bacteria. Here, we determined the immunogenic activity of recombinant ChoD from Mtb in a mouse model. We found that peritoneal exudate cells obtained from mice injected i.p. with ChoD but not those from mice injected with PBS responded in vitro with highly spontaneous, as well as phorbol 12-myristate 13-acetate (PMA)-stimulated, production of reactive oxygen species (ROS). However, ChoD significantly reduced the ROS response to PMA in re-stimulated cells in vitro. The cytokine secretion pattern in mice immunized s.c. with ChoD emulsified with incomplete Freund's adjuvant (IFA) showed evidence of Th2-induced or proinflammatory immune responses. The main cytokines detected in sera were interleukin (IL) 6 and 5, tumour necrosis factor α (TNF-α) and monocyte chemoattractant protein 1, while IL-2 and IL-12 as well as interferon γ were undetectable. Similarly, ChoD protein alone activated THP-1-derived macrophages to release proinflammatory IL-6, IL-8 and TNF-α, in vitro. Moreover, a statistically significant predominance of the IgG1 isotype over that of IgG2a in the sera of mice immunized with ChoD/IFA was observed. In conclusion, we demonstrated here that ChoD of Mtb is an active protein, which is able to induce the immune response both in vivo and in vitro.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:228 |
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| Enthalten in: |
Immunology letters - 228(2020) vom: 10. Dez., Seite 103-111 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Szulc-Kielbik, Izabela [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.11.2021 Date Revised 18.11.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.imlet.2020.11.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM317342711 |
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| 041 | |a eng | ||
| 100 | 1 | |a Szulc-Kielbik, Izabela |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Determination of in vitro and in vivo immune response to recombinant cholesterol oxidase from Mycobacterium tuberculosis |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 18.11.2021 | ||
| 500 | |a Date Revised 18.11.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Cholesterol oxidase (ChoD) is an enzyme that is involved but is dispensable in the process of cholesterol degradation by Mycobacterium tuberculosis (Mtb). Interestingly, ChoD is a virulence factor of Mtb, and it strongly modulates the function of human macrophages in vitro, allowing the intracellular survival of bacteria. Here, we determined the immunogenic activity of recombinant ChoD from Mtb in a mouse model. We found that peritoneal exudate cells obtained from mice injected i.p. with ChoD but not those from mice injected with PBS responded in vitro with highly spontaneous, as well as phorbol 12-myristate 13-acetate (PMA)-stimulated, production of reactive oxygen species (ROS). However, ChoD significantly reduced the ROS response to PMA in re-stimulated cells in vitro. The cytokine secretion pattern in mice immunized s.c. with ChoD emulsified with incomplete Freund's adjuvant (IFA) showed evidence of Th2-induced or proinflammatory immune responses. The main cytokines detected in sera were interleukin (IL) 6 and 5, tumour necrosis factor α (TNF-α) and monocyte chemoattractant protein 1, while IL-2 and IL-12 as well as interferon γ were undetectable. Similarly, ChoD protein alone activated THP-1-derived macrophages to release proinflammatory IL-6, IL-8 and TNF-α, in vitro. Moreover, a statistically significant predominance of the IgG1 isotype over that of IgG2a in the sera of mice immunized with ChoD/IFA was observed. In conclusion, we demonstrated here that ChoD of Mtb is an active protein, which is able to induce the immune response both in vivo and in vitro | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cholesterol oxidase | |
| 650 | 4 | |a Cytokines | |
| 650 | 4 | |a Mouse peritoneal exudate cells | |
| 650 | 4 | |a Mycobacterium tuberculosis | |
| 650 | 4 | |a Th1/Th2 response | |
| 650 | 7 | |a Adjuvants, Immunologic |2 NLM | |
| 650 | 7 | |a Bacterial Proteins |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a Inflammation Mediators |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 650 | 7 | |a Virulence Factors |2 NLM | |
| 650 | 7 | |a Freund's Adjuvant |2 NLM | |
| 650 | 7 | |a 9007-81-2 |2 NLM | |
| 650 | 7 | |a Cholesterol Oxidase |2 NLM | |
| 650 | 7 | |a EC 1.1.3.6 |2 NLM | |
| 700 | 1 | |a Brzostek, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Gatkowska, Justyna |e verfasserin |4 aut | |
| 700 | 1 | |a Kielbik, Michal |e verfasserin |4 aut | |
| 700 | 1 | |a Klink, Magdalena |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Immunology letters |d 1983 |g 228(2020) vom: 10. Dez., Seite 103-111 |w (DE-627)NLM012603953 |x 1879-0542 |7 nnns |
| 773 | 1 | 8 | |g volume:228 |g year:2020 |g day:10 |g month:12 |g pages:103-111 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.imlet.2020.11.002 |3 Volltext |
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