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

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-4Ra^-/- 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, and BALF was used for multiplex cytokine analysis.

RESULTS: Anti-Mpn and P1-specific total IgG responses were decreased in allergen-sensitized, infected animals compared to unsensitized, infected controls (p < 0.01). Decreased titers of IgG1, IgG2a, IgG2b and IgG3 were present in rP1-specific, but not OVA-specific IgG subclass levels in sensitized, infected mice. Loss of IL-4Ra signaling partially restored anti-bacterial IgG responses in IgG2a and IgG2b subclasses.

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-4Ra^-/- animals.