Partial Depletion of Regulatory T Cells Enhances Host Inflammatory Response Against Acute Pseudomonas aeruginosa Infection After Sepsis

• Published in: Inflammation 2018-10, Vol.41 (5), p.1780-1790
• Main Authors: Hu, Zhi-qiang, Yao, Yong-ming, Chen, Wei, Bian, Jia-lan, Zhao, Lin-jun, Chen, Long-wang, Hong, Guang-liang, Lu, Zhong-qiu, Zhao, Guang-ju
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Load; Biomedical and Life Sciences; Biomedicine; CD25 antigen; Cecum; Coinfection - immunology; Cytokines - metabolism; Immunology; Immunoregulation; Immunosuppression; Infections; Inflammation; Inflammation - immunology; Interleukin 10; Interleukin 6; Internal Medicine; Lung Injury; Lungs; Lymphocyte Depletion; Lymphocytes T; Mice; Models, Biological; Original Article; Pathology; Pharmacology/Toxicology; Pseudomonas aeruginosa; Pseudomonas aeruginosa - immunology; Pseudomonas Infections - immunology; Rheumatology; Secondary infection; Sepsis; Sepsis - complications; Spleen; T-Lymphocytes, Regulatory - immunology
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-018-0821-8

Immune dysfunction contributes to secondary infection and worse outcomes in sepsis. Regulatory T cells (Tregs) have been implicated in sepsis-induced immunosuppression. Nevertheless, the role of Tregs in secondary infection after sepsis remains to be determined. In the present study, a two-hit model which mimics clinical conditions was used and the potential role of Tregs in secondary Pseudomonas aeruginosa infection post-sepsis was investigated. Results showed that mice were susceptible to secondary P. aeruginosa infection 3 days, but not 7 days, post-cecal ligation and puncture (CLP). The levels of IL-17A, IL-1β, and IL-6 remained low in CLP mice after P. aeruginosa infection, while the levels of IL-10 increased significantly. Additionally, increased number of Tregs in both lung and spleen was observed in “two-hit” mice. Injection with PC61 (anti-CD25) mAb reduced the number of Tregs by 50% in spleen and 60% in lung of septic mice. This partial depletion of Tregs elevated IL-17A, IL-1β, and IL-6 production and decreased IL-10 levels in septic mice with P. aeruginosa infection, leading to lower bacterial load, attenuation of lung injury, and improvement of survival. The present findings demonstrate that Tregs play a crucial role in secondary P. aeruginosa infection after sepsis by modulating the inflammatory response.