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Transient Decrease of Circulating and Tissular Dendritic Cells in Patients With Mycobacterial Disease and With Partial Dominant IFNγR1 Deficiency.
Frontiers in Immunology ( IF 7.3 ) Pub Date : 2020-05-12 , DOI: 10.3389/fimmu.2020.01161
Laura Dotta 1 , Donatella Vairo 2 , Mauro Giacomelli 3 , Daniele Moratto 2 , Nicola Tamassia 4 , William Vermi 5 , Silvia Lonardi 5 , Jean-Laurent Casanova 6, 7, 8, 9, 10 , Jacinta Bustamante 6, 7, 8, 11 , Silvia Giliani 2 , Raffaele Badolato 12
Affiliation  

Interferon-γ receptor 1 (IFNγR1) deficiency is one of the inborn errors of IFN-γ immunity underlying Mendelian Susceptibility to Mycobacterial Disease (MSMD). This molecular circuit plays a crucial role in regulating the interaction between dendritic cells (DCs) and T lymphocytes, thus affecting DCs activation, maturation, and priming of T cells involved in the immune response against intracellular pathogens. We studied a girl who developed at the age of 2.5 years a Mycobacterium avium infection characterized by disseminated necrotizing granulomatous lymphadenitis, and we compared her findings with other patients with the same genetic condition. The patient carried a heterozygous 818del4 mutation in the IFNGR1 gene responsible of autosomal dominant (AD) partial IFNγR1 deficiency. During the acute infection blood cells immunophenotyping showed a marked reduction in DCs counts, including both myeloid (mDCs) and plasmacytoid (pDCs) subsets, that reversed after successful prolonged antimicrobial therapy. Histology of her abdomen lymph node revealed a profound depletion of tissue pDCs, as compared to other age-matched granulomatous lymphadenitis of mycobacterial origin. Circulating DCs depletion was also observed in another patient with AD partial IFNγR1 deficiency during mycobacterial infection. To conclude, AD partial IFNγR1 deficiency can be associated with a transient decrease in both circulating and tissular DCs during acute mycobacterial infection, suggesting that DCs counts monitoring might constitute a useful marker of treatment response.



中文翻译:

分枝杆菌病和部分显性IFNγR1缺乏症患者的循环树突状细胞短暂减少。

干扰素-γ受体1(IFNγR1)的缺乏是孟德尔对分枝杆菌病(MSMD)易感性的IFN-γ免疫的先天错误之一。该分子回路在调节树突状细胞(DC)和T淋巴细胞之间的相互作用中起着至关重要的作用,从而影响参与针对细胞内病原体的免疫反应的T细胞的DC激活,成熟和启动。我们研究了一个2.5岁以下的女孩鸟分枝杆菌以散发性坏死性肉芽肿性淋巴结炎为特征的感染,我们将她的发现与其他遗传条件相同的患者进行了比较。该患者携带了一个杂合的818del4突变。干扰素GR1该基因负责常染色体显性(AD)部分IFNγR1缺乏。在急性感染过程中,血细胞的免疫表型显示DC计数显着降低,包括髓样(mDC)和浆细胞样(pDC)子集,在成功进行长时间的抗微生物治疗后,这种计数会逆转。与其他年龄相匹配的分枝杆菌肉芽肿性淋巴结炎相比,她的腹部淋巴结的组织学检查显示,组织pDC大量耗竭。在分枝杆菌感染期间另一例患有AD部分IFNγR1缺乏症的患者中也观察到循环DC的消耗。总而言之,AD部分IFNγR1缺乏可能与急性分枝杆菌感染期间循环DC和组织DC的短暂减少有关,这表明DC计数监测可能是治疗反应的有用标志。

更新日期:2020-06-26
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