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

Ivana Palucci, Michela Sali, Giovanni Delogu, Alessandro Salustri, Flavio De Maio, Delia Goletti, L. Petrone, Fabiola Ciccosanti, Vincent Bondet, Darragh Duffy, Gian Maria Fimia, D. Goletti

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)299-306
Number of pages8
JournalInternational Journal of Medical Microbiology
Volume309
DOIs
Publication statusPublished - 2019

Keywords

  • Adult
  • Biological Assay
  • Blood Cells
  • CXCL-10
  • CXCR3
  • Chemokine CXCL10
  • Host directed therapy
  • Humans
  • IP-10
  • Male
  • Mycobacteria
  • Mycobacterium tuberculosis
  • Nontuberculous Mycobacteria
  • Personalized medicine
  • Tuberculosis
  • Tumor Cells, Cultured

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