Inhaled granulocyte-macrophage colony-stimulating factor for Mycobacterium abscessus in cystic fibrosis

Nontuberculous mycobacteria (NTM) are an important emerging threat to cystic fibrosis (CF) patients. In North America, where the incidence of NTM in CF patients is ≥11.8%, Mycobacterium abscessus complex (MABSC), a multidrug-resistant NTM, accounts for ~35% of these [1], is notoriously recognised as difficult to eradicate, and seriously affects morbidity and mortality in CF [2] as well as lung transplantation outcomes [3, 4]. The mechanisms for the increased incidence of MABSC infection in CF patients are not known. The immune response in CF patients is directed to the Th2 response, which is associated with poorer clinical outcome and accelerated decline in lung function. This Th2 pattern is associated with diminished interferon- production and lesser activation of macrophages. One activator of macrophages is granulocyte–macrophage colony-stimulating factor (GM-CSF), the Toll-like receptor activation of which includes phagocytosis, bactericidal activity, oxidative burst and cell adhesion in macrophages [5]. Two experimental findings support the plausibility that reduced GM-CSF-elicited macrophage activation may contribute to NTM and MABSC infection in CF. First, alveolar macrophages from in GM-CSF–/– mice exhibit defective phagocytosis, bacterial killing and reduced H2O2 production [6]. Second, although wild-type mouse models of M. abscessus pulmonary infection show limited morbidity and are limited in their usefulness to study NTM therapy GM-CSF knockout...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Original Articles: Research letters Source Type: research