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.

γ-干扰素诱导蛋白10（IP-10）是一种有效的化学引诱剂，可促进单核细胞和活化的T细胞向炎症灶的迁移。慢性丙型肝炎病毒（HCV）和肺结核（TB）感染患者的血清中IP-10升高，尽管IP-10在限制结核分枝杆菌（Mtb）复制中的作用尚待确定。在这里，我们使用人全血（WB）检测的离体模型研究了IP-10对分枝杆菌复制的影响。特别是，我们比较了用不同的Mtb感染后IP-10的水平非结核分枝杆菌（NTM）的临床菌株和种类，并评估IP-10如何包含细菌复制。有趣的是，我们观察到对宿主酶二肽基肽酶IV（DPP-IV）的抑制（通过在趋化因子N端裂解两个氨基酸来使IP-10失活）限制了分枝杆菌在WB中的持久性，支持了完整的关键作用。 IP-10介导抗Mtb的长度回复。加入真核细胞表达的重组IP-10增强了WB中的抗分枝杆菌活性，尽管当添加IP-10含有不同比例的裂解和非裂解形式的趋化因子时，没有观察到差异。而且，重组IP-10没有发挥直接的抗分枝杆菌作用。我们的结果强调了IP-10在分枝杆菌发病机理中的临床相关性，并支持通过靶向IP-10 / CXCR3途径作为宿主定向疗法治疗Mtb或NTM感染而可能获得的潜在结果。