Allergic Airway Sensitization Impairs Anti-Bacterial IgG Antibody Responses During Bacterial Respiratory Infections

Publication date: Available online 6 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Arthur H. Totten, Li Xiao, Danlin Luo, David Briles, Joanetha Y. Hale, Donna M. Crabb, Trenton R. Schoeb, Ammar Saadoon Alishlash, Ken B. Waites, T. Prescott Atkinson

Abstract

Background

Mycoplasma pneumoniae (Mpn), an atypical human pathogen, has been associated with asthma initiation and exacerbation. Asthmatics have been reported to have higher carriage rates of Mpn compared to non-asthmatics, and are at greater risk for invasive respiratory infections.

Objective

To study whether prior allergen sensitization affects the host response to chronic bacterial infection.

Methods

BALB/cJ and IL-4Rα^-/- mice were sensitized with ovalbumin (OVA), and then infected with Mpn or Streptococcus pneumoniae (Spn). Immune parameters were analyzed at 30 days post-infection and included cellular profiles in bronchoalveolar lavage (BAL), and serum IgG and IgE antibody levels to whole bacterial lysate, recombinant P1 (rP1) adhesin, and OVA. Total lung RNA was examined for transcript levels and BAL fluid for cytokine protein profiles.

Results

Anti-Mpn antibody responses were decreased in allergen-sensitized, Mpn-infected animals compared to controls, but OVA-specific IgG responses were unaffected. Similar decreases in anti-Spn antibody levels were found in OVA-sensitized animals. However, Mpn, but not Spn, infection augmented anti-OVA IgE antibody responses. Loss of IL-4 receptor signaling partially restored anti-Mpn antibody responses in IgG2a and IgG2b subclasses. Inflammatory cytokine levels in BAL fluid from OVA-sensitized, Mpn- or Spn-infected animals were reduced compared to uninfected OVA-sensitized controls. Unexpectedly, airway hyperreactivity to methacholine was essentially ablated in Mpn-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, e.g. Mpn, can augment ongoing allergic responses and inhibit pulmonary T2 cytokine responses and allergic airway hyperreactivity.

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