A Case for Antibiotic Perturbation of the Microbiota Leading to Allergy Development

Lisa A Reynolds; B Brett Finlay

Disclosures

Expert Rev Clin Immunol. 2013;9(11):1019-1030. 

In This Article

Quality of Bacterial Signaling

In many situations, the quality of signals from the microbiota, rather than the total bacterial load, has been shown to influence immune responses in the steady state or in murine disease models. Mice treated with either ampicillin, metronidazole, vancomycin or neomycin all harbored substantial shifts in fecal populations compared with untreated mice.[38] Following infection with A/PR8 influenza virus, however, only neomycin-treated mice had reduced numbers of influenza-specific CD8+ T cells,[38] suggesting that neomycin-sensitive bacteria are important for priming adaptive immunity to this pathogen. Similarly, vancomycin treatment, yet not streptomycin treatment, during the early period of life results in enhanced airway inflammation in an ovalbumin-driven model of experimental asthma.[57] Human studies have also revealed that different classes of antibiotic present different risks. One study found no association between sulfonamide administration and asthma,[49] whereas the use of macrolide[60] or cephalosporins[52,60] has been marked as a predictor of later asthma development, suggesting that shifting the microbiota in specific ways differentially affects the potential for disease development.

Individual species within the microbiota differ in their ability to stimulate immune responses, and the frequency of specific motifs within their DNA correlates with their capacity to activate LP dendritic cells (DCs).[61] The composition of the microbiota will dictate the production of metabolites which can alter immune responsiveness,[62] and the composition of PAMPs which differentially signal through TLRs. Signaling through TLRs has been shown both to limit the differentiation of Tregs, in the case of TLR9,[26] or promote Treg differentiation, in the case of TLR2.[63] Thus, a microbiota rich in ligands for a certain TLR could alter the regulatory capacity of the host immune system. Although human data are contradictory, several studies have correlated TLR polymorphisms with serum IgE levels and asthma development.[64]

It should be noted that both the absence, as well as the presence of specific bacterial groups within the microbiota dictates the resulting immune system activation status, as specific components of the microbiota are also crucial for limiting arms of the immune response.[31,63]

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