© 2018 American Academy of Allergy, Asthma & Immunology Background: Mycoplasma pneumoniae, an atypical human pathogen, has been associated with asthma initiation and exacerbation. Asthmatic patients have been reported to have higher carriage rates of M pneumoniae compared with nonasthmatic subjects and are at greater risk for invasive respiratory infections. Objective: We sought to study whether prior allergen sensitization affects the host response to chronic bacterial infection. Methods: BALB/cJ and IL-4 receptor α −/− mice were sensitized with ovalbumin (OVA) and then infected with M pneumoniae or Streptococcus pneumoniae. Immune parameters were analyzed at 30 days postinfection and included cellular profiles in bronchoalveolar lavage fluid (BALF) and serum IgG and IgE antibody levels to whole bacterial lysate, recombinant P1 adhesin, and OVA. Total lung RNA was examined for transcript levels, and BALF was examined for cytokine protein profiles. Results: Anti–M pneumoniae antibody responses were decreased in allergen-sensitized, M pneumoniae–infected animals compared with control animals, but OVA-specific IgG responses were unaffected. Similar decreases in anti–S pneumoniae antibody levels were found in OVA-sensitized animals. However, M pneumoniae, but not S pneumoniae, infection augmented anti-OVA IgE antibody responses. Loss of IL-4 receptor signaling partially restored anti–M pneumoniae antibody responses in IgG 2a and IgG 2b subclasses. Inflammatory cytokine levels in BALF from OVA-sensitized, M pneumoniae–infected or S pneumoniae–infected animals were reduced compared with those in uninfected OVA-sensitized control animals. Unexpectedly, airway hyperreactivity to methacholine was essentially ablated in M pneumoniae–infected, OVA-sensitized animals. Conclusions: An established type 2–biased host immune response impairs the host immune response to respiratory bacterial infection in a largely pathogen-independent manner. Some pathogens, such as M pneumoniae, can augment ongoing allergic responses and inhibit pulmonary type 2 cytokine responses and allergic airway hyperreactivity.