A Novel Encochleated Formulation Improves Atovaquone Activity in a Murine Model of Pneumocystis Pneumonia.
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ABSTRACT:
SUBMITTER: Cushion MT
PROVIDER: S-EPMC8280485 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
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A Novel Encochleated Formulation Improves Atovaquone Activity in a Murine Model of Pneumocystis Pneumonia.
Cushion Melanie T MT Kumar Parag P Lu Ruying R Ashbaugh Alan A Adeojo Lilian W LW Alfaro Raul R Mannino Raphael R Tramont Edmund E Kovacs Joseph A JA
The Journal of infectious diseases 20210701 2
Although atovaquone is effective in treating and preventing Pneumocystis pneumonia (PCP), its use is limited by nonlinear absorption and adverse events. The current study was undertaken to examine the activity of encochleated atovaquone (eATQ), a novel lipid-crystal nanoparticle formulation, in a mouse model of PCP. eATQ 100-200 mg was superior to commercially available atovaquone at 14 days in decreasing total Pneumocystis nuclei and asci. eATQ plus anidulafungin reduced nuclei significantly be ...[more]
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2020-12-24 | GSE159562 | GEO
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Project description:RationaleInfection with Pneumocystis, an opportunistic fungal pathogen, can result in fulminant pneumonia in the clinical setting of patients with immunosuppression. In murine models, Pneumocystis has previously been shown to induce a CD4+ T cell-dependent eosinophilic response in the lung capable of providing protection.ObjectivesWe sought to explore the role of Pneumocystis in generating asthma-like lung pathology, given the natural eosinophilic response to infection.MethodsPneumocystis infection or antigen treatment was used to induce asthma-like pathology in wild-type mice. The roles of CD4+ T cells and eosinophils were examined using antibody depletion and knockout mice, respectively. The presence of anti-Pneumocystis antibodies in human serum samples was detected by ELISA and Western blotting.Measurements and main resultsPneumocystis infection generates a strong type II response in the lung that requires CD4+ T cells. Pneumocystis infection was capable of priming a Th2 response similar to that of a commonly studied airway allergen, the house dust mite. Pneumocystis antigen treatment was also capable of inducing allergic inflammation in the lung, resulting in anti-Pneumocystis IgE production, goblet cell hyperplasia, and increased airway resistance. In the human population, patients with severe asthma had increased levels of anti-Pneumocystis IgG and IgE compared with healthy control subjects. Patients with severe asthma with elevated anti-Pneumocystis IgG levels had worsened symptom scores and lung parameters such as decreased forced expiratory volume and increased residual volume compared with patients with severe asthma who had low anti-Pneumocystis IgG.ConclusionsThe present study demonstrates for the first time, to our knowledge, that Pneumocystis is an airway allergen capable of inducing asthma-like lung pathology.
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