Neutrophil and Eosinophil DNA Extracellular Trap Formation: Lessons From Pathogenic Fungi.

Fungal infections represent a worldwide health problem. Fungal pathogens are responsible for a variety of conditions, including superficial diseases, allergic pathologies and potentially lethal invasive infections. Neutrophils and eosinophils have been implicated as effector cells in several pathologies. Neutrophils are major effector cells involved in the control of fungal infections and exhibit a plethora of antifungal mechanisms, such as phagocytosis, reactive oxygen species production, degranulation, extracellular vesicle formation, and DNA extracellular trap (ET) release. Eosinophils are polymorphonuclear cells classically implicated as effector cells in the pathogenesis of allergic diseases and helminthic infections, although their roles as immunomodulatory players in both innate and adaptive immunity are currently recognized. Eosinophils are also endowed with antifungal activities and are abundantly found in allergic conditions associated with fungal colonization and sensitization. Neutrophils and eosinophils have been demonstrated to release their nuclear and mitochondrial DNA in response to many pathogens and pro-inflammatory stimuli. ETs have been implicated in the killing and control of many pathogens, as well as in promoting inflammation and tissue damage. The formation of ETs by neutrophils and eosinophils has been described in response to pathogenic fungi. Here, we provide an overview of the mechanisms involved in the release of neutrophil and eosinophil ETs in response to fungal pathogens. General implications for understanding the formation of ETs and the roles of ETs in fungal infections are discussed.

Elastase modifies bleomycin-induced pulmonary fibrosis in mice.

Pulmonary fibrosis (PF) is characterized by excessive accumulation of collagen in the lungs. Emphysema is characterized by loss of the extracellular matrix (ECM) and alveolar enlargement. We studied the co-participation of elastase-induced mild emphysema in bleomycin-induced PF in mice by analyzing oxidative stress, inflammation and lung histology. C57BL/6 mice were divided into four groups: control; bleomycin (0.1U/mouse); elastase (using porcine pancreatic elastase (PPE)+bleomycin (3U/mouse 14 days before 0.1U/mouse of bleomycin; PPE+B); elastase (3U/mouse). Mice were humanely sacrificed 7, 14 and 21 days after treatment with bleomycin or vehicle. PF was observed 14 days and 21 days after bleomycin treatment but was observed after 14 days only in the PPE+B group. In the PPE+B group at 21 days, we observed many alveoli and alveolar septa with few PF areas. We also observed marked and progressive increases of collagens 7, 14 and 21 days after bleomycin treatment whereas, in the PPE+B group, collagen deposition was observed only at 14 days. There was a reduction in activities of the antioxidant enzymes superoxide dismutase (p<0.05), catalase (p<0.01) and glutathione peroxidase (p<0.01) parallel with an increase in nitrite (p<0.01) 21 days after bleomycin treatment compared with the control group. These endpoints were also reduced (p<0.05, p<0.05 and p<0.01, respectively) and increased (p<0.01) in the PPE+B group at 21 days compared with the control group. Interleukin (IL)-1ß expression was upregulated (p<0.01) whereas IL-6 was downregulated (p<0.05) in the PPE+B group at 21 days compared with the control group. PF and emphysema did not coexist in our model of lung disease and despite increased levels of oxidative stress and inflammatory markers after combined stimulus (elastase and bleomycin) overall histology was improved to that of the nearest control group.

Toll-like receptors (TLR2 and TLR4) recognize polysaccharides of Pseudallescheria boydii cell wall.

Pseudallescheria boydii is an opportunistic fungus widespread in the environment, and has recently emerged as an agent of localized as well as disseminated infections in both immunocompromised and immunocompetent hosts. The host response to fungi is in part dependent on the activation of evolutionary conserved receptors including Toll-like receptors and phagocytic receptors. This review will discuss the isolation and structural characterization of α-glucans and rhamnomannans from P. boydii cell wall and their roles in the induction of innate immune response.