Abstract
The prevalence of atopic diseases has been steadily increasing since the mid twentieth century, a rise that has been linked to modern hygienic lifestyles that limit exposure to microbes and immune system maturation. Overactive type 2 CD4+ helper T (Th2) cells are known to be closely associated with atopy and represent a key target for treatment. In this study, we present an initial characterization of ammonia oxidizing bacteria (AOB) Nitrosomonas eutropha D23, an environmental microbe that is not associated with human pathology, and show AOB effectively suppress the polarization of Th2 cells and production of Th2-associated cytokines (IL-5, IL-13, and IL-4) by human peripheral blood mononuclear cells (PBMC). We show that AOB inhibit Th2 cell polarization not through Th1-mediated suppression, but rather through mechanisms involving the anti-inflammatory cytokine IL-10 and the potential inhibition of dendritic cells, as evidenced by a reduction in Major Histocompatibility Complex Class II (MHC II) and CD86 expression following AOB treatment. This is the first report of immunomodulatory properties of AOB, and provides initial support for the development of AOB as a potential therapeutic for atopic diseases.
Highlights
Reduced exposure to non-commensal microbes, early in life, as well as a loss of biodiversity within the human microbiome has been associated with a topy[5,6,7,8]
To test the effect of ammonia oxidizing bacteria (AOB) on immune responses, we developed a co-culture model with human peripheral blood mononuclear cells (PBMC) derived from healthy subjects
AOB were added to PBMC at a ratio of four bacteria per PBMC for 72 h
Summary
Reduced exposure to non-commensal microbes, early in life, as well as a loss of biodiversity within the human microbiome has been associated with a topy[5,6,7,8]. W620, were shown to shift T cell polarization towards a Th1 response via dendritic cell conditioning[6,19,20,21] These cowshed bacteria highlight the potential to identify novel immuno-modulatory bacteria from farm environments. Farm soils frequently contain high concentrations of ammonium due to animal waste and fertilizers, and are niches containing ammonia oxidizing bacteria (AOB)[22,23]. These soil chemolithoautotrophic Gram negative bacteria play a critical role in the global nitrogen c ycle[22]. We postulated that AOB could play a role in the human microbiome’s ability to regulate the immune response
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