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

Abstract:

: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.

journal_name

Inflammation

journal_title

Inflammation

authors

Hu ZQ,Yao YM,Chen W,Bian JL,Zhao LJ,Chen LW,Hong GL,Lu ZQ,Zhao GJ

doi

10.1007/s10753-018-0821-8

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

1780-1790

issue

5

eissn

0360-3997

issn

1573-2576

pii

10.1007/s10753-018-0821-8

journal_volume

41

pub_type

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