IP-10 contributes to the inhibition of mycobacterial growth in an ex vivo whole blood assay
Copyright © 2019 Elsevier GmbH. All rights reserved..
Interferon-γ inducible protein 10 (IP-10), is a potent chemoattractant that promotes migration of monocytes and activated T-cells to inflammation foci. IP-10 is elevated in serum of patients with chronic hepatitis C virus (HCV) and tuberculosis (TB) infections, although it remains to be determined the contribution of IP-10 in restricting Mycobacterium tuberculosis (Mtb) replication. Here, we investigated the impact of IP-10 on mycobacteria replication using the ex vivo model of human whole-blood (WB) assay. In particular, we compared the levels of IP-10 upon infection with different Mtb clinical strains and species of non-tuberculous mycobacteria (NTM) and evaluated how IP-10 may contain bacterial replication. Interestingly, we observed that the inhibition of the host enzyme dipeptidyl peptidase IV (DPP-IV), which inactivates IP-10 through cleavage of two amino acids at the chemokine N-terminus, restricted mycobacterial persistence in WB, supporting the critical role of full length IP-10 in mediating an anti-Mtb response. Addition of recombinant IP-10 expressed in eukaryotic cells enhanced the anti-mycobacterial activity in WB, although no differences were observed when IP-10 containing different proportions of cleaved and non-cleaved forms of the chemokine were added. Moreover, recombinant IP-10 did not exert a direct anti-mycobacterial effect. Our results underscore the clinical relevance of IP-10 in mycobacteria pathogenesis and support the potential outcomes that may derive by targeting the IP-10/CXCR3 pathway as host directed therapies for the treatment of Mtb or NTM infections.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:309 |
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| Enthalten in: |
International journal of medical microbiology : IJMM - 309(2019), 5 vom: 27. Juli, Seite 299-306 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Palucci, Ivana [VerfasserIn] |
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| Links: |
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| Themen: |
CXCL-10 |
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| Anmerkungen: |
Date Completed 21.11.2019 Date Revised 21.11.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijmm.2019.05.005 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM297649558 |
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| 520 | |a Interferon-γ inducible protein 10 (IP-10), is a potent chemoattractant that promotes migration of monocytes and activated T-cells to inflammation foci. IP-10 is elevated in serum of patients with chronic hepatitis C virus (HCV) and tuberculosis (TB) infections, although it remains to be determined the contribution of IP-10 in restricting Mycobacterium tuberculosis (Mtb) replication. Here, we investigated the impact of IP-10 on mycobacteria replication using the ex vivo model of human whole-blood (WB) assay. In particular, we compared the levels of IP-10 upon infection with different Mtb clinical strains and species of non-tuberculous mycobacteria (NTM) and evaluated how IP-10 may contain bacterial replication. Interestingly, we observed that the inhibition of the host enzyme dipeptidyl peptidase IV (DPP-IV), which inactivates IP-10 through cleavage of two amino acids at the chemokine N-terminus, restricted mycobacterial persistence in WB, supporting the critical role of full length IP-10 in mediating an anti-Mtb response. Addition of recombinant IP-10 expressed in eukaryotic cells enhanced the anti-mycobacterial activity in WB, although no differences were observed when IP-10 containing different proportions of cleaved and non-cleaved forms of the chemokine were added. Moreover, recombinant IP-10 did not exert a direct anti-mycobacterial effect. Our results underscore the clinical relevance of IP-10 in mycobacteria pathogenesis and support the potential outcomes that may derive by targeting the IP-10/CXCR3 pathway as host directed therapies for the treatment of Mtb or NTM infections | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CXCL-10 | |
| 650 | 4 | |a CXCR3 | |
| 650 | 4 | |a Host directed therapy | |
| 650 | 4 | |a IP-10 | |
| 650 | 4 | |a Mycobacteria | |
| 650 | 4 | |a Personalized medicine | |
| 650 | 4 | |a Tuberculosis | |
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| 700 | 1 | |a Battah, Basem |e verfasserin |4 aut | |
| 700 | 1 | |a Salustri, Alessandro |e verfasserin |4 aut | |
| 700 | 1 | |a De Maio, Flavio |e verfasserin |4 aut | |
| 700 | 1 | |a Petrone, Linda |e verfasserin |4 aut | |
| 700 | 1 | |a Ciccosanti, Fabiola |e verfasserin |4 aut | |
| 700 | 1 | |a Sali, Michela |e verfasserin |4 aut | |
| 700 | 1 | |a Bondet, Vincent |e verfasserin |4 aut | |
| 700 | 1 | |a Duffy, Darragh |e verfasserin |4 aut | |
| 700 | 1 | |a Fimia, Gian Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Goletti, Delia |e verfasserin |4 aut | |
| 700 | 1 | |a Delogu, Giovanni |e verfasserin |4 aut | |
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