Dynamics of Macrophage, T and B Cell Infiltration Within Pulmonary Granulomas Induced by Mycobacterium tuberculosis in Two Non-Human Primate Models of Aerosol Infection.

Dynamics of Macrophage, T and B Cell Infiltration Within Pulmonary Granulomas Induced by Mycobacterium tuberculosis in Two Non-Human Primate Models of Aerosol Infection.
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DOI:
10.3389/fimmu.2021.776913
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发表时间:
2021
影响因子:
7.3
通讯作者:
Salguero FJ
Salguero FJ
中科院分区:
医学2区
文献类型:
--
作者:
Hunter L;Hingley-Wilson S;Stewart GR;Sharpe SA;Salguero FJ

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结核病的非人灵长类动物模型是结核病实验领域中最常用的模型之一,因为它们密切模仿人类结核病的整个疾病进展谱。然而,肺肉芽肿的早期细胞相互作用仍不清楚。使用该模型可以研究肺肉芽肿内细胞的早期相互作用,这在人类样本中是无法进行的。将感染后两个时间点的恒河猴和食蟹猴肺肉芽肿分为1 - 6类(早期至晚期肉芽肿),采用免疫组化方法鉴定CD68+巨噬细胞、CD3+ T细胞和CD20+ B细胞。多核巨细胞和抗酸杆菌也被定量。在感染后第4周,除1类肉芽肿外,食蟹猕猴的CD68+细胞比恒河猴多。食蟹蟹在1型肉芽肿中CD20+ B细胞的比例也明显较高。感染后第12周,两种动物的4类和5类肉芽肿中CD68+细胞最多;但两者间无显著性差异。在大多数肉芽肿类型中,食蟹的CD3+ T细胞和CD20+ B细胞含量明显高于恒河猴。攻毒后第12周多核巨细胞和抗酸杆菌在第5类和第6类中数量最多。本研究确定了恒河猴和食蟹猴肺肉芽肿中免疫细胞的基本细胞组成和空间分布随时间的变化。这项研究的数据将增加这一领域已经获得的知识,并可能为结核病疫苗和治疗方法的未来研究提供信息。
Non-human primate models of Tuberculosis (TB) are one of the most commonly used within the experimental TB field because they closely mimic the whole spectrum of disease progression of human TB. However, the early cellular interactions of the pulmonary granuloma are still not well understood. The use of this model allows investigation into the early interactions of cells within pulmonary granulomas which cannot be undertaken in human samples. Pulmonary granulomas from rhesus and cynomolgus macaques from two timepoints post infection were categorised into categories 1 – 6 (early to late stage granulomas) and immunohistochemistry was used to identify CD68+ macrophages, CD3+ T cells and CD20+ B cells. Multinucleated giant cells and acid-fast bacilli were also quantified. At week four post infection, cynomolgus macaques were found to have more CD68+ cells than rhesus in all but category 1 granulomas. Cynomolgus also had a significantly higher percentage of CD20+ B cells in category 1 granulomas. At week twelve post infection, CD68+ cells were most abundant in category 4 and 5 granulomas in both species; however, there were no significant differences between them. CD3+ T cells and CD20+ B cells were significantly higher in the majority of granuloma categories in cynomolgus compared to rhesus. Multinucleated giant cells and acid-fast bacilli were most abundant in categories 5 and 6 at week 12 post challenge in both species. This study has identified the basic cellular composition and spatial distribution of immune cells within pulmonary granulomas in both rhesus and cynomolgus macaques over time. The data from this study will add to the knowledge already gained in this field and may inform future research on vaccines and therapeutics for TB.
DOI: 10.1371/journal.ppat.1009410
发表时间: 2021-03
期刊: PLoS pathogens
影响因子: 6.7
作者:
Queval CJ;Fearns A;Botella L;Smyth A;Schnettger L;Mitermite M;Wooff E;Villarreal-Ramos B;Garcia-Jimenez W;Heunis T;Trost M;Werling D;Salguero FJ;Gordon SV;Gutierrez MG
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影响因子: 5.2
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发表时间: 2019-11-01
影响因子: 7.3
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