Marti Hanna, Koschwanez Maria, Pesch Theresa, Blenn Christian, Borel Nicole
Institute of Veterinary Pathology, University of Zurich-Vetsuisse, Zurich, Switzerland.
Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland.
PLoS One. 2014 Jul 14;9(7):e102239. doi: 10.1371/journal.pone.0102239. eCollection 2014.
New therapeutic strategies are needed to overcome drawbacks in treatment of infections with intracellular bacteria. Chlamydiaceae are Gram-negative bacteria implicated in acute and chronic diseases such as abortion in animals and trachoma in humans. Water-filtered infrared A (wIRA) is short wavelength infrared radiation with a spectrum ranging from 780 to 1400 nm. In clinical settings, wIRA alone and in combination with visible light (VIS) has proven its efficacy in acute and chronic wound healing processes. This is the first study to demonstrate that wIRA irradiation combined with VIS (wIRA/VIS) diminishes recovery of infectious elementary bodies (EBs) of both intra- and extracellular Chlamydia (C.) in two different cell lines (Vero, HeLa) regardless of the chlamydial strain (C. pecorum, C. trachomatis serovar E) as shown by indirect immunofluorescence and titration by subpassage. Moreover, a single exposure to wIRA/VIS at 40 hours post infection (hpi) led to a significant reduction of C. pecorum inclusion frequency in Vero cells and C. trachomatis in HeLa cells, respectively. A triple dose of irradiation (24, 36, 40 hpi) during the course of C. trachomatis infection further reduced chlamydial inclusion frequency in HeLa cells without inducing the chlamydial persistence/stress response, as ascertained by electron microscopy. Irradiation of host cells (HeLa, Vero) neither affected cell viability nor induced any molecular markers of cytotoxicity as investigated by Alamar blue assay and Western blot analysis. Chlamydial infection, irradiation, and the combination of both showed a similar release pattern of a subset of pro-inflammatory cytokines (MIF/GIF, Serpin E1, RANTES, IL-6, IL-8) and chemokines (IL-16, IP-10, ENA-78, MIG, MIP-1α/β) from host cells. Initial investigation into the mechanism indicated possible thermal effects on Chlamydia due to irradiation. In summary, we demonstrate a non-chemical reduction of chlamydial infection using the combination of water-filtered infrared A and visible light.
需要新的治疗策略来克服细胞内细菌感染治疗中的缺点。衣原体是革兰氏阴性细菌，与动物流产和人类沙眼等急性和慢性疾病有关。水过滤红外A（wIRA）是一种短波长红外辐射，光谱范围为780至1400纳米。在临床环境中，单独使用wIRA以及与可见光（VIS）联合使用已证明其在急性和慢性伤口愈合过程中的疗效。这是第一项证明wIRA照射与VIS联合使用（wIRA/VIS）可减少两种不同细胞系（Vero、HeLa）中细胞内和细胞外衣原体（C.）感染性原体（EBs）恢复的研究，无论衣原体菌株如何（C. pecorum、沙眼衣原体血清型E），间接免疫荧光和传代滴定法均表明如此。此外，在感染后40小时（hpi）单次暴露于wIRA/VIS分别导致Vero细胞中C. pecorum包涵体频率和HeLa细胞中沙眼衣原体的显著降低。沙眼衣原体感染过程中的三次照射剂量（24、36、40 hpi）进一步降低了HeLa细胞中的衣原体包涵体频率，且未诱导衣原体持续存在/应激反应，电子显微镜检查证实了这一点。通过Alamar蓝试验和蛋白质印迹分析研究发现，照射宿主细胞（HeLa、Vero）既不影响细胞活力，也不诱导任何细胞毒性分子标记物。衣原体感染、照射以及两者的组合显示宿主细胞释放促炎细胞因子（MIF/GIF、丝氨酸蛋白酶抑制剂E1、RANTES、IL-6、IL-8）和趋化因子（IL-16、IP-10、ENA-78、MIG、MIP-1α/β）的模式相似。对机制的初步研究表明，照射可能对衣原体产生热效应。总之，我们证明了使用水过滤红外A和可见光联合可实现衣原体感染的非化学性减少。
