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潜伏性结核患者产生干扰素-γ的CD5⁺ B细胞频率增加,这些细胞对分枝杆菌蛋白有高效反应。

Latent Tuberculosis Patients Have an Increased Frequency of IFN-γ-Producing CD5+ B Cells, Which Respond Efficiently to Mycobacterial Proteins.

作者信息

Flores-Gonzalez Julio, Ramón-Luing Lucero A, Romero-Tendilla Jesus, Urbán-Solano Alexia, Cruz-Lagunas Alfredo, Chavez-Galan Leslie

机构信息

Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080, Mexico.

Laboratory of Immunobiology and Genetic, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080, Mexico.

出版信息

Pathogens. 2023 Jun 9;12(6):818. doi: 10.3390/pathogens12060818.

Abstract

Tuberculosis (TB) remains a public health problem worldwide and is one of the deadliest infectious diseases, only after the current COVID-19 pandemic. Despite significant advances in the TB field, there needs to be more immune response comprehension; for instance, the role played by humoral immunity is still controversial. This study aimed to identify the frequency and function of B1 and immature/transitional B cells in patients with active and latent TB (ATB and LTB, respectively). Here we show that LTB patients have an increased frequency of CD5+ B cells and decreased CD10+ B cells. Furthermore, LTB patients stimulated with mycobacteria's antigens increase the frequency of IFN-γ-producing B cells, whereas cells from ATB do not respond. Moreover, under the mycobacterial protein stimulus, LTB promotes a pro-inflammatory environment characterized by a high level of IFN-γ but also can produce IL-10. Regarding the ATB group, they cannot produce IFN-γ, and mycobacterial lipids and proteins stimulate only the IL-10 production. Finally, our data showed that in ATB, but not in LTB, B cell subsets correlate with clinical and laboratory parameters, suggesting that these CD5+ and CD10+ B cell subpopulations have the potential to be biomarkers to differentiate between LTB and ATB. In conclusion, LTB has increased CD5+ B cells, and these cells can maintain a rich microenvironment of IFN-γ, IL-10, and IL-4. In contrast, ATB only maintains an anti-inflammatory environment when stimulated with mycobacterial proteins or lipids.

摘要

结核病(TB)仍然是一个全球性的公共卫生问题,并且是最致命的传染病之一,仅次于当前的新冠疫情。尽管结核病领域取得了重大进展,但仍需要对免疫反应有更多的了解;例如,体液免疫所起的作用仍存在争议。本研究旨在确定活动性结核病和潜伏性结核病患者(分别为ATB和LTB)中B1细胞以及未成熟/过渡性B细胞的频率和功能。我们在此表明,LTB患者的CD5⁺ B细胞频率增加,而CD10⁺ B细胞减少。此外,用分枝杆菌抗原刺激的LTB患者会增加产生IFN-γ的B细胞频率,而ATB患者的细胞则无反应。此外,在分枝杆菌蛋白刺激下,LTB会促进以高水平IFN-γ为特征的促炎环境,但也能产生IL-10。对于ATB组,它们不能产生IFN-γ,分枝杆菌脂质和蛋白仅刺激IL-10的产生。最后,我们的数据表明,在ATB中而非LTB中,B细胞亚群与临床和实验室参数相关,这表明这些CD5⁺和CD10⁺ B细胞亚群有可能成为区分LTB和ATB的生物标志物。总之,LTB患者的CD5⁺ B细胞增加,并且这些细胞可以维持富含IFN-γ、IL-10和IL-4的微环境。相比之下,ATB在用分枝杆菌蛋白或脂质刺激时仅维持抗炎环境。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fde6/10304593/30b3d40e0c6b/pathogens-12-00818-g001.jpg

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