Department of Infectious Disease, Imperial College London, London, United Kingdom.
Leishmaniasis Research and Treatment Centre, University of Gondar, Ethiopia.
PLoS Negl Trop Dis. 2022 Aug 15;16(8):e0010681. doi: 10.1371/journal.pntd.0010681. eCollection 2022 Aug.
Visceral leishmaniasis (VL) patients co-infected with HIV (VL/HIV patients) experience frequent treatment failures, VL relapses, opportunistic infections, and higher mortality. Their immune system remains profoundly suppressed after clinical cure and they maintain higher parasite load. This is in contrast with patients with VL alone (VL patients). Since neutrophils play a critical role in the control of Leishmania replication and the regulation of immune responses, we tested the hypothesis that neutrophil activation status and effector functions are fully restored in VL, but not in VL/HIV patients. Our results show the neutrophil counts and all activation markers and effector functions tested in our study were reduced at the time of diagnosis in VL and VL/HIV patients as compared to controls. CD62L, CD63, arginase 1 expression levels and reactive oxygen species production were restored at the end of treatment in both groups. However, neutrophil counts, CD10 expression and phagocytosis remained significantly lower throughout follow-up in VL/HIV patients; suggesting that dysregulated neutrophils contribute to the impaired host defence against pathogens in VL/HIV patients.
内脏利什曼病(VL)合并人类免疫缺陷病毒(HIV)感染的患者(VL/HIV 患者)经常出现治疗失败、VL 复发、机会性感染和更高的死亡率。他们的免疫系统在临床治愈后仍然受到严重抑制,并且维持着更高的寄生虫负荷。这与单独患有 VL(VL 患者)的患者形成对比。由于中性粒细胞在控制利什曼原虫复制和调节免疫反应中起着关键作用,我们检验了这样一个假设,即中性粒细胞的激活状态和效应功能在 VL 中得到完全恢复,但在 VL/HIV 患者中没有。我们的研究结果表明,与对照组相比,VL 和 VL/HIV 患者在诊断时的中性粒细胞计数以及我们研究中测试的所有激活标志物和效应功能均降低。在两组患者中,CD62L、CD63、精氨酸酶 1 表达水平和活性氧物质的产生在治疗结束时均得到恢复。然而,在整个随访期间,VL/HIV 患者的中性粒细胞计数、CD10 表达和吞噬作用仍然显著降低;这表明功能失调的中性粒细胞可能导致 VL/HIV 患者宿主对病原体的防御受损。