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.

FIG. 1.

Percentage of mice found to have M. pneumoniae in BAL fluid by culture or PCR after intranasal inoculation with M. pneumoniae.

FIG. 2.

Histopathologic appearance (magnification, ×100) of control mouse lung 530 days after inoculation with SP4 broth (A) compared with that of lung showing inflammation 530 days after inoculation with M. pneumoniae (B).

FIG. 3.

Baseline Penh (prior to methacholine challenge) after inoculation (Inoc) with SP4 broth or M. pneumoniae (Mp). A box plot with outliers is shown: vertical boxes represent 25 to 75 percentiles; error bars represent 10 to 90 percentiles, and lines in vertical boxes represent median values.

FIG. 4.

Penh with aerosolized methacholine challenge after inoculation (Inoc) with SP4 broth or M. pneumoniae (Mp). A box plot with outliers is shown: vertical boxes represent 25 to 75 percentiles, error bars represent 10 to 90 percentiles, and lines in vertical boxes represent median values.

FIG. 5.

M. pneumoniae IgG titers 109, 150, 245, 368, and 530 days after inoculation with M. pneumoniae. Each point represents one mouse.

FIG. 6.

Correlation between M. pneumoniae IgG titers and HPS 530 days after inoculation with M. pneumoniae.