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

• DOI: 10.1007/s10753-018-0821-8
• Publication Date: 2018-06-28T04:18:08Z
• Authors: Zhi-qiang Hu; Yong-ming Yao; Wei Chen; Jia-lan Bian; Lin-jun Zhao; Long-wang Chen; Guang-liang Hong; Zhong-qiu Lu; Guang-ju Zhao
• Keywords: Inflammation; 0303 health sciences; Coinfection; Lung Injury; Models, Biological; T-Lymphocytes, Regulatory; Bacterial Load; Lymphocyte Depletion; 3. Good health; Mice; 03 medical and health sciences; Sepsis; Pseudomonas aeruginosa; Animals; Cytokines; Pseudomonas Infections

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.