Loss of IL-4Rα signaling is partially able to restore anti-Mycoplasma pneumoniae IgG titers during allergic airway disease

Abstract

Abstract Rationale Mycoplasma pneumoniae (Mpn) is the leading bacterial agent of pediatric community acquired pneumonia. Epidemiologic evidence has suggested increased susceptibility to Mpn infection among asthmatics. We hypothesized that allergic airway sensitization would impair host immune responses to Mpn infection, but that loss of Th2 cytokine signals (IL-4, IL-13) would overcome this impairment in a murine model. Methods Wild type (Wt) and IL-4Rα−/− BALB/cJ mice were sensitized and challenged with ovalbumin (OVA) to induce allergic airway inflammation, and then infected with Mpn. Immune parameters were studied by analysis of cellular profiles in bronchoalveolar lavage fluid (BALF), serum IgG and IgE antibody levels to a whole bacterial antigen preparation, recombinant Mpn P1 adhesin (rP1), and OVA. Total lung RNA was used to examine cytokine transcript levels for Th1, Th2 and Th17 biasing transcripts. Results Anti-Mpn and P1-specific total IgG responses were decreased in allergen-sensitized animals compared to unsensitized controls (p < 0.01). Decreased titers of IgG1, IgG2a, IgG2b and IgG3 were present in rP1-specific, but not OVA-specific IgG subclass levels. Loss of IL-4Rα signaling partially restores total and subclass-specific responses. Th2 cytokine mRNA levels were increased in Wt, but not IL-4Rα−/− OVA sensitized groups compared to controls. IL-4Rα−/− animals had increased Interferon-γ(IFN-γ) and IL-17A mRNA levels compared to Wt animals. Conclusions Anti-Mpn IgG antibody titers were decreased in Wt allergic animals compared to unsensitized controls and the impairment in immune response to the pathogen was partially restored by inhibition of Th2 signaling in IL-4Rα−/− animals.