Lung epithelial GM-CSF improves host defense function and epithelial repair in influenza virus pneumonia-a new therapeutic strategy?

Barbara Rösler,Susanne Herold

doi:10.1186/s40348-016-0055-5

Abstract

Influenza viruses (IVs) circulate seasonally and are a common cause of respiratory infections in pediatric and adult patients. Additionally, recurrent pandemics cause massive morbidity and mortality worldwide. Infection may result in rapid progressive viral pneumonia with fatal outcome. Since accurate treatment strategies are still missing, research refocuses attention to lung pathology and cellular crosstalk to develop new therapeutic options.Alveolar epithelial cells (AECs) play an important role in orchestrating the pulmonary antiviral host response. After IV infection they release a cascade of immune mediators, one of which is granulocyte and macrophage colony-stimulating factor (GM-CSF). GM-CSF is known to promote differentiation, activation and mobilization of myeloid cells. In the lung, GM-CSF drives immune functions of alveolar macrophages and dendritic cells (DCs) and also improves epithelial repair processes through direct interaction with AECs. During IV infection, AEC-derived GM-CSF shows a lung-protective effect that is also present after local GM-CSF application. This mini-review provides an overview on GM-CSF-modulated immune responses to IV pneumonia and its therapeutic potential in severe IV pneumonia.

Highlights

Respiratory viral infections are often seen in pediatric patients [1]
Apart from respiratory syncytial virus (RSV) and other respiratory viruses, influenza virus (IV) infection is a common cause of acute respiratory failure on pediatric intensive care units (ICUs) [2]
granulocyte and macrophage colony-stimulating factor (GM-CSF) expressed by hyperplastic type II alveolar epithelial cell (AEC) mediates accumulation of neighboring CD1a+ dendritic cell (DC) in inflamed lungs [42]. These findings suggest that GM-CSF is beneficial and operative in humans

Summary

Introduction

Respiratory viral infections are often seen in pediatric patients [1]. They may cause primary viral pneumonia that may progress to lung failure with fatal outcome. T cell-produced interferon ɣ (IFN ɣ) during course of infection effected augmented FcɣR levels on alveolar macrophages which in turn stimulated IFN ɣ production by secretion of inflammatory cytokines (interleukin (IL)-18, IL-12), linking innate and adaptive immunity in a positive feedback loop.

Results

Conclusion