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Alterations in NETosis impairs immunity in patients with hereditary hemorrhagic telangiectasia (HHT)
Objectives Clinical studies demonstrated that patients with HHT suffer from an elevated susceptibility to bacterial infections. As neutrophil granulocytes (neutrophils) are crucial innate immune cells that provide the first line of defense against bacterial pathogens, changes in the activity of these cells were analyzed in patients with HHT.
Methods Neutrophil granulocytes of HHT patients and healthy donors were characterized. The release of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) was evaluated. Moreover, their cytoskeleton organization and migratory capacity were assessed.
Results Neutrophil granulocytes from 9 HHT patients and 7 healthy controls with no significant differences in age and sex were analyzed (age: Mann-Whitney U-test, p = 0.87; sex: Χ2 = 0.12, p = 0.73). The migratory capacity and the ability to release ROS were comparable between healthy and HHT neutrophils, with or without stimulation with Phorbol-12-myristat-13-acetat (PMA) or bacteria (Pseudomonas aeruginosa) (chemotaxis Index: p = 0.07; ROS-release: p =0.61; Mann-Whitney U-test). Notably, we have observed significantly lower amounts of F-actin in neutrophils in patients with HHT, as compared to healthy controls (Mann-Whitney U-test: p ≤ 0.05). Even though the spontaneous NET release was only slightly reduced in HHT patients, NETosis in response to P. aeruginosa infection was significantly suppressed in such patients (Mann-Whitney U-test: p = 0.002).
Conclusions For the first time we could demonstrate that, neutrophils form HHT patients have an impaired ability to release NETs, possibly due to structural changes in the cytoskeleton organization. This could be responsible for the enhanced susceptibility of these patients to recurring bacterial infections.
10 June 2020 (online)
© Georg Thieme Verlag KG
Stuttgart · New York