Innate-Like Lymphocytes Are Immediate Participants in the Hyper-Acute Immune Response to Trauma and Hemorrhagic Shock.

Joanna Manson,Shuhua Chen,Timothy R Billiar,Mostafa H Ramadan,Rosemary Hoffman

doi:10.3389/fimmu.2019.01501

Abstract

Adverse outcomes following severe traumatic injury are frequently attributed to a state of immunological dysfunction acquired during treatment and recovery. Recent genomic evidence however, suggests that the trajectory toward development of multiple organ dysfunction syndrome (MODS) is already in play at admission (<2 h following injury). Improved understanding of the molecular events during the hyper-acute immunological response to trauma, <2 h following injury, may reveal opportunities to ameliorate organ injury and expedite recovery. Lymphocytes have not previously been considered key participants in this early response; however, two observations in human trauma patients namely, raised populations of circulating NKT and NK cells during the hyper-acute phase and persistent lymphopenia beyond 48 h show association with the development of MODS during recovery. These highlight the need for greater understanding of lymphocyte function in the hyper-acute phase of inflammation. An exploratory study was therefore conducted in a well-established murine model of trauma and hemorrhagic shock (T&HS) to investigate (1) the development of lymphopenia in the murine model and (2) the phenotypic and functional changes of three innate-like lymphocyte subsets, NK1.1+ CD3–, NK1.1+ CD3+, γδTCR+ CD3+ cells, focusing on the first 6 h following injury. Rapid changes in phenotype and function were demonstrated in these cells within blood and spleen, but responses in lung tissue lagged behind. This study describes the immediacy of the innate-like lymphocyte response to trauma in different body compartments and considers new lines for further investigation to develop our understanding of MODS pathogenesis.

Highlights

Severe traumatic injury activates an acute inflammatory response, which increases in extent and magnitude during the first 24 h after injury [1, 2]
This study used a well-established murine model of trauma and hemorrhagic shock (T&HS) to define the dynamics of lymphopenia and examine innatelike lymphocyte behavior within different organs, at structured intervals following injury
It confirms that lymphopenia occurs between 2 and 6 h in this murine model, which supports human observations and suggests murine work is of value to this line of investigation [10, 11, 15]

Summary

Introduction

Severe traumatic injury activates an acute inflammatory response, which increases in extent and magnitude during the first 24 h after injury [1, 2]. Organ support is the mainstay of MODS management, resulting in long critical care admissions, late in-hospital deaths and long-term ill-health in some survivors [6, 8, 9] These adverse outcomes after trauma have, to date, been attributed to an acquired immunological dysfunction which develops during recovery, recent evidence has demonstrated that the trajectory toward MODS development is already in-play at admission [1, 5, 10, 11]. If persistent after 48 h, lymphopenia is associated with MODS development and increased in-hospital mortality [11, 15] These data suggest that lymphocytes, innate-like lymphocytes, play a significant role in the immunological events immediately following injury; much earlier than previously thought. The events in other compartments and the influence of cell mobilization have not yet been considered in clinical studies

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