Antibiotics induce polarization of pleural macrophages to M2-like phenotype in patients with tuberculous pleuritis

• Main Authors: Wang, Sisi (Author), Zhang, Jian (Author), Sui, Liyan (Author), Xu, Hao (Author), Piao, Qianling (Author), Qu, Xinglong (Author), Sun, Ying (Author), Song, Lei (Author), Peng, Liping (Author), Hua, Shucheng (Author), Hu, Guangan (Contributor), Chen, Jianzhu (Contributor), Li, Dan 1969- (Author), Liu, Ying, Ph. D. Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science (Author)
• Other Authors: Koch Institute for Integrative Cancer Research at MIT (Contributor)
• Format: Article
• Language: English
• Published: Nature Publishing Group, 2017-12-11T18:59:31Z.
• Subjects: Article
• Online Access: Get fulltext

 Pleural macrophages play critical roles in pathogenesis of tuberculous pleuritis, but very little is known about their response to anti-tuberculosis antibiotics treatment. Here, we examined whether and how pleural macrophages change in phenotype, transcription and function following antibiotics treatment in patients with tuberculous pleuritis. Results show pro-inflammatory cytokines were down-regulated significantly post antibiotic treatment in the pleural effusions and pleural macrophages up-regulated markers characteristic of M2 macrophages such as CD163 and CD206. Differential expression analysis of transcriptomes from four paired samples before and after treatment identified 230 treatment-specific responsive genes in pleural macrophages. Functional analysis identified interferon-related pathway to be the most responsive genes and further confirmed macrophage polarization to M2-like phenotype. We further demonstrate that expression of a significant fraction of responsive genes was modulated directly by antibiotics in pleural macrophages in vitro. Our results conclude that pleural macrophages polarize from M1-like to M2-like phenotype within a mean of 3.5 days post antibiotics treatment, which is dependent on both pleural cytokine environment and direct modulatory effects of antibiotics. The treatment-specific genes could be used to study the roles of pleural macrophages in the pathogenesis of tuberculous pleuritis and to monitor the response to antibiotics treatment.