Background Over 40% of chronic stable asthma patients have evidence of respiratory Mycoplasma pneumoniae (Mp) infection as detected by PCR, but not by serology and culture, suggesting that a low-level Mp is involved in chronic asthma. However, the role of such a low-level Mp infection in the regulation of allergic inflammation remains unknown.
Objective To determine the impact of a low-level Mp infection in mice with established airway allergic inflammation on allergic responses such as eosinophilia and chemokine eotaxin-2, and the underlying mechanisms [i.e. the prostaglandin E2 (PGE2) pathway] since PGE2 inhalation before an allergen challenge suppressed the eosinophil infiltration in human airways.
Methods BALB/c mouse models of ovalbumin (OVA)-induced allergic asthma with an ensuing low- or high-dose Mp were used to assess IL-4 expression, bronchoalveolar lavage (BAL) eosinophil, eotaxin-2 and PGE2 levels, and lung mRNA levels of microsomal prostaglandin E synthase-1 (mPGES-1). Primary alveolar macrophages (pAMs) from naïve BALB/c mice were cultured to determine whether Mp-induced PGE2 or exogenous PGE2 down-regulates IL-4/IL-13-induced eotaxin-2.
Results Low-dose Mp in allergic mice significantly enhanced IL-4 and eotaxin-2, and moderately promoted lung eosinophilia, whereas high-dose Mp significantly reduced lung eosinophilia and tended to decrease IL-4 and eotaxin-2. Moreover, in both OVA-naïve and allergic mice, lung mPGES-1 mRNA and BAL PGE2 levels were elevated in mice infected with high-dose, but not low-dose Mp. In pAMs, IL-4/IL-13 significantly increased eotaxin-2, which was reduced by Mp infection accompanied by dose-dependent PGE2 induction. Exogenous PGE2 inhibited IL-4/IL-13-induced eotaxin-2 in a dose-dependent manner.
Conclusions This study highlights a novel concept on how different bacterial loads in the lung modify the established allergic airway inflammation and thus interact with an allergen to further induce Th2 responses. That is, unlike high-level Mp, low-level Mp fails to effectively induce PGE2 to down-regulate allergic responses (e.g. eotaxin-2), thus maintaining or even worsening allergic inflammation in asthmatic airways.