Mycoplasma pneumoniae Induces Chronic Respiratory Infection, Airway Hyperreactivity, and Pulmonary Inflammation: a Murine Model of Infection-Associated Chronic Reactive Airway Disease

Abstract

Because chronic Mycoplasma pneumoniae respiratory infection is hypothesized to play a role in asthma, the potential of M. pneumoniae to establish chronic respiratory infection with associated pulmonary disease was investigated in a murine model. BALB/c mice were intranasally inoculated once with M. pneumoniae and examined at 109, 150, 245, 368, and 530 days postinoculation. M. pneumoniae was detected in bronchoalveolar lavage fluid by culture or PCR in 70 and 22% of mice at 109 and 530 days postinoculation, respectively. Lung histopathology was normal up to 368 days postinoculation. At 530 days, however, 78% of the mice inoculated with M. pneumoniae demonstrated abnormal histopathology characterized by peribronchial and perivascular mononuclear infiltrates. A mean histopathologic score (HPS) at 530 days of 5.1 was significantly greater (P < 0.01) than that for controls (HPS score of 0). Serum anti-M. pneumoniae immunoglobulin G was detectable in all of the mice inoculated with M. pneumoniae and was inversely correlated with HPS (r ‫؍‬ ؊0.95, P ‫؍‬ 0.01) at 530 days postinoculation. Unrestrained whole-body plethysmography measurement of enhanced pause revealed significantly elevated airway methacholine reactivity in M. pneumoniae-inoculated mice compared with that in controls at 245 days (P ‫؍‬ 0.03) and increased airway obstruction at 530 days (P ‫؍‬ 0.01). Murine M. pneumoniae respiratory infection can lead to chronic pulmonary disease characterized by airway hyperreactivity, airway obstruction, and histologic inflammation.While Mycoplasma pneumoniae is known to be a significant cause of acute respiratory illness in children and adults, the significance of chronic infection is undetermined. In humans, M. pneumoniae is reported to commonly be detectable by culture of the respiratory tract for up to several months after clinical recovery from acute pneumonia (5). Even after therapy with effective antibiotics, such as erythromycin or tetracycline, M. pneumoniae can still be cultured from respiratory secretions (6, 18). After receiving macrolides for 14 days, children have been found to have pulmonary structural abnormalities, by high-resolution computed tomography, suggestive of small airway obstruction 1 to 2 years after M. pneumoniae pneumonia with significantly increased frequency compared with that of controls. In these children, a greater antimycoplasma antibody titer was a significant risk factor for the development of abnormal pulmonary sequelae, suggesting that the host immune response may play a pathogenic role in this condition (10). The duration of M. pneumoniae infection in the human lower respiratory tract after acute pneumonia as determined by a method more sensitive than culture, such as PCR, has not been investigated in a controlled fashion.Of potentially greater relevance, chronic M. pneumoniae respiratory infection has been hypothesized to play a role in asthma. By PCR, M. pneumoniae has been detected in the lower airways of chronic, stable asthmatics with significantly greater frequency than in ...

Atypical pathogens and respiratory tract infections

“…Evidence from in vitro animal studies indicates that atypical respiratory pathogens may play a role in the pathogenesis of the disease [92]. Mice infected with M. pneumoniae, for example, can develop a chronic pulmonary infection characterised by airway hypersensitivity, airway obstruction and histological inflammation, which lends support to the notion that M. pneumoniae infection may cause chronic pulmonary disease with functional airway obstruction, as seen in asthma patients [94].…”

Mycoplasma pneumoniae CARDS Toxin Induces Pulmonary Eosinophilic and Lymphocytic Inflammation

“…Although peak histopathological score occurred at 7 days after toxin exposure ( Figure 2F), M. pneumoniae infection of the mouse is known to have a prolonged impact on the pulmonary compartments (13). To evaluate the course of pathological changes after a single exposure to rCARDS toxin, additional mice were treated with 700 pmol of rCARDS or CF intranasally, and lungs were harvested 14, 28, and 56 days after exposure.…”

“…A number of studies have highlighted the importance of IL-12 and IFN-g and Th-1 type T-cell responses during the pathogenesis of M. pneumoniae infection in mouse models of pneumonia (8,(12)(13)(14). However, if the host is sensitized to allergen before infection, M. pneumoniae can worsen asthma-like disease in mouse models, leading to airway remodeling, mucus metaplasia, and changes in pulmonary function (15,16).…”

SPLUNC1 Promotes Lung Innate Defense Against Mycoplasma pneumoniae Infection in Mice

“…13 Lung tissues were embedded in paraffin, cut in 4-m thick sections, and stained with H&E. The stained lung sections were evaluated in a double-blind fashion under a light microscope using a histopathologic inflammatory scoring system as described previously in a hamster model of Mp infection 14 and mouse models of Mp infection. [15][16][17] A final score per mouse, both infected and uninfected, on a scale of 0 to 26 (least to most severe) was obtained based on assessment of the quantity and quality of peribronchiolar and peribronchial inflammatory infiltrates, luminal exudates, perivascular infiltrates, and parenchymal pneumonia.…”