Prenatal initiation of endotoxin airway exposure prevents subsequent allergen-induced sensitization and airway inflammation in mice

Background

New preventive strategies against the development of allergic diseases focus on potentially immunomodulatory components, such as bacterial LPSs. Optimal time frames for initiating immunomodulation to receive a sufficient effect against allergen sensitization are still unclear.

Objective

Using a mouse model, we investigated the influence of prenatal LPS exposure on later allergen-mediated sensitization and airway inflammation in the offspring.

Methods

Pregnant BALB/c mice were repeatedly exposed to aerosolized LPS (LPS Escherichia coli; 3× per week, day 7 of gestation time up to delivery). Some of the offspring were further exposed to aerosolized LPS before allergen sensitization with ovalbumin (OVA; administered intraperitoneally day 28 up to day 42) and OVA airway challenges (days 56-58). Positive control animals were placebo exposed to PBS instead of LPS, and negative control animals were first placebo exposed and later placebo sensitized with PBS instead of OVA.

Results

Compared with positive control animals, prenatal LPS exposure suppressed (1) allergen-specific sensitization (IgE production), (2) eosinophilic airway inflammation (reduced numbers of eosinophils in bronchoalveolar lavage fluids), and (3) in vivo airway reactivity in response to methacholine. These effects occurred only when prenatal was combined with further postnatal LPS exposure. Suppression of allergen-mediated inflammatory responses was associated with increased Toll-like receptor and T-bet expression by lung tissues and a shift toward predominantly T_H1 immune responses in spleen cells cultured with OVA in vitro.

Conclusion

Prenatal initiated and postnatal sustained LPS exposure increased endotoxin susceptibility and prevented later allergen sensitization in offspring through inhibition of T_H2 immune responses.

Clinical implications

Immunomodulation with bacterial compounds during gestation time might be an effective mode for first-step primary prevention against allergic diseases.

Key words: Asthma, cytokines, lipopolysaccharides, mice, ovalbumin

Abbreviations used: AI, Airway inflammation, AR, Airway reactivity, CD62L, L-selectin, ConA, Concanavalin A, DC, Dendritic cell, LBP, LPS-binding protein, MCh, Methacholine, MNC, Mononuclear cell, OVA, Ovalbumin, Penh, Enhanced pause, sCD14, Soluble CD14, TLR, Toll-like receptor, Treg cell, T regulatory cell