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IP-10 contributes to the inhibition of mycobacterial growth in an ex vivo whole blood assay

Abstract : 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02173495
Contributor : Marie-Christine Vougny <>
Submitted on : Thursday, July 4, 2019 - 2:58:04 PM
Last modification on : Monday, January 13, 2020 - 5:08:18 PM

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Ivana Palucci, Basem Battah, Alessandro Salustri, Flavio de Maio, Linda Petrone, et al.. IP-10 contributes to the inhibition of mycobacterial growth in an ex vivo whole blood assay. International Journal of Medical Microbiology, Elsevier, In press, ⟨10.1016/j.ijmm.2019.05.005⟩. ⟨pasteur-02173495⟩

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