Identification of cGAS as an innate immune sensor of extracellular bacterium Pseudomonas aeruginosa.

Cyclic GMP-AMP synthase (cGAS) is reported essential for detecting intracellular bacteria. However, it remains to be determined whether and how cGAS is involved in extracellular bacterial infection. Here, we report that cGAS is essential for mediating type I interferon (IFN) production in infection by multiple extracellular pathogens, including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus. In addition, the canonical cGAS-stimulator of interferon gene (STING)-IFN axis is required for protecting mice from P. aeruginosa-induced mouse acute pulmonary infection, confirmed in cGAS pathway-specific gene deficiency mouse models. cGAS -/- and STING -/- mice exhibited reduced type I IFNs production, excessive inflammatory response accompanied with decreased resistance to P. aeruginosa challenge. Unfolded protein response was also modulated by cGAS through IRF3 and type I IFNs under P. aeruginosa infection. Collectively, these findings uncover the importance of cGAS in initiating immune responses against extracellular bacterial infection.

[Efficacy comparison of different stimulation therapies for periarthritis of shoulder].

OBJECTIVE: To compare clinical efficacy differences among electroacupuncture (EA), transcutaneous electrical nerve stimulation (TENS) therapy and acupoint massage (AM) on periarthritis of shoulder. METHODS: One hundred and twenty cases were randomly divided into an EA group, a TENS group and an AM group, 40 cases in each one. The selection of acupoints in the three groups were all the same, which were Jianqian (Extra), Xiabai (LU 4), Jianyu (LI 15), Binao (LI 14), Jianliao (TE 14), Naohui (TE 13), Xiaohai (SI 8) and Houxi (SI 3). EA was applied in the EA group with dense-disperse wave for 30 min, TENS therapy with dense-disperse wave for 30 min in the TENS group and AM combined with mobilization manipulation of Tuina on the shoulder in the AM group. All of the treatment was given once a day, six times a week and totally 4 weeks were required. The score of visual analogue scale (VAS) and improvement of shoulder joint activities in the three groups before and after the treatment were observed. RESULTS: After the treatment, the VAS score and activities of shoulder joint were all improved in the three groups (all P < 0.001) and AM group had more obvious improvement than TENS group and EA group (all P < 0.05). The effective and curative rate was 61.50 (24/39) in the AM group, which was superior to 42.9% (15/35) in the EA group and 44.4% (16/36) in the TENS group (both P < 0.05). The effective and curative rate of shoulder joint activities in the AM group was 61.5% (24/39), which was superior to 48.6% (17/35) in the EA group and 44.4% (16/36) in the TENS group (both P < 0.05). CONCLUSION: The acupoint massage has obvious clinical efficacy on periarthritis of shoulder, which could effectively relieve the pain and improve activities of shoulder joint, and it is superior to EA and TENS therapy.