Regulation of Sepsis and Endotoxic Shock by Regulatory T cells
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Date
2013-07, 2014-07
Authors
Okeke, Emeka B
Journal Title
Journal ISSN
Volume Title
Publisher
Wolters Kluwer Health Lippincott Williams & Wilkins
American Association of Immunologists
American Association of Immunologists
Abstract
One of the major challenges facing clinicians is how to effectively manage excessive host immune response to pathogenic insults resulting in sepsis. This is demonstrated by the fact that despite over half-century research efforts, sepsis and its spectrum of diseases (severe sepsis and septic shock) are still associated with poor clinical outcome. Currently, sepsis is a leading cause of death in intensive care units.
The immune system protects the host against pathogens and is therefore armed with an arsenal of deadly ammunitions (including chemicals, cells and proteins) necessary for the elimination of microbes. It is therefore paramount that the immune system must develop mechanisms necessary to prevent destruction of the host it is designed to protect. A good example of such a mechanism is found in the subset of lymphocytes known as regulatory T cells (Tregs). There is unequivocal experimental evidence of the role of Tregs in the maintenance of immune homeostasis and self tolerance and aberrant Treg function has been linked with several inflammatory diseases. Since sepsis is a disease marked by a hyper-inflammatory state, I investigated the possible role of Tregs in dampening sepsis-induced excessive inflammation.
Using a murine model of lipopolysaccharide (LPS) infusion and bacterial infection, I show that Tregs are essential for survival during sepsis because their depletion leads to acute death to an otherwise non-lethal dose of LPS. This enhanced susceptibility to LPS following Treg depletion was also observed using live E. coli infection. Next, I probed the mechanism by which Tregs protect against LPS challenge. I found that defective Treg function leads to exaggerated activity of two immune cells – CD4+ effector T cells and neutrophils in response to LPS, leading to severe inflammatory response. Hence, this work successfully illustrates the critical role of Tregs in regulating other immune cells and the catastrophic consequences of defective Treg function during an immune response.
Overall, this work highlights the significant role of Tregs in the regulation of bacteria associated inflammatory processes. The findings hold implications for the successful management of sepsis and have potential for use in development of adequate therapeutic intervention for sepsis.
Description
Keywords
Immunology, Bacterial Infection, Immune Regulation, Septic Shock
Citation
Shock. 2013 Jul;40(1):65-73
J Immunol. 2014 Jul 15;193(2):655-62
J Immunol. 2014 Jul 15;193(2):655-62