Abstract
Mycoplasma pneumoniae causes a range of airway and extrapulmonary pathologies in humans. Clinically, M. pneumoniae is associated with acute exacerbations of human asthma and a worsening of experimentally induced asthma in mice. Recently, we demonstrated that Community Acquired Respiratory Distress Syndrome (CARDS) toxin, an ADP-ribosylating and vacuolating toxin synthesized by M. pneumoniae, is sufficient to induce an asthma-like disease in BALB/cJ mice. To test the potential of CARDS toxin to exacerbate preexisting asthma, we examined inflammatory responses to recombinant CARDS toxin in an ovalbumin (OVA) murine model of asthma. Differences in pulmonary inflammatory responses between treatment groups were analyzed by histology, cell differentials and changes in cytokine and chemokine concentrations. Additionally, assessments of airway hyperreactivity were evaluated through direct pulmonary function measurements. Analysis of histology revealed exaggerated cellular inflammation with a strong eosinophilic component in the CARDS toxin-treated group. Heightened T-helper type-2 inflammatory responses were evidenced by increased expression of IL-4, IL-13, CCL17 and CCL22 corresponding with increased airway hyperreactivity in the CARDS toxin-treated mice. These data demonstrate that CARDS toxin can be a causal factor in the worsening of experimental allergic asthma, highlighting the potential importance of CARDS toxin in the etiology and exacerbation of human asthma.
Highlights
Asthma is a chronic disease characterized by reversible airway obstruction, inflammation, and airway hyperreactivity (AHR) [1]
We have shown that exposure of naıve BALB/cJ mice to rCARDS toxin resulted in an eosinophilic-rich peribronchiolar and perivascular cellular inflammation, resembling asthma [19,22]
To test the capacity of Community Acquired Respiratory Distress Syndrome (CARDS) toxin to exacerbate preexisting asthma-like inflammation, BALB/cJ mice were treated with OVA and challenged with rCARDS toxin 48 hours after the last OVA challenge, at the peak of OVA-induced allergic inflammation
Summary
Asthma is a chronic disease characterized by reversible airway obstruction, inflammation, and airway hyperreactivity (AHR) [1]. While the causes of asthma are multi-factorial, asthma exacerbations can be triggered by viral or bacterial infections leading to greater morbidity [2,3,4,5,6,7,8]. Mycoplasma pneumoniae is a common human bacterial pathogen that causes acute or chronic respiratory infections and is linked to a variety of extrapulmonary infections or sequelae [2,9,10]. M. pneumoniae infection and its impact on pre-existing allergic inflammation have been tested in mouse models of asthma. These studies demonstrate the capacity of M. pneumoniae to exacerbate many features associated with allergic inflammation including T-helper type 2 (Th2) responses and AHR [17,18]
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