The ammonia oxidizing bacterium Nitrosomonas eutropha D23 blocks T helper 2 cell polarization via IL-10 mediated interference with dendritic cell activation

Abstract

ABSTRACTThe prevalence of atopic diseases has been steadily increasing since the mid 20th 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 report that the ammonia oxidizing bacteria (AOB) Nitrosomonas eutropha D23, an environmental microbe that is not associated with human pathology, effectively suppresses the polarization of Th2 cells and production of Th2-associated cytokines (IL-5, IL-13, & 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 an IL-10-mediated mechanism that interferes with the activation 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 supports the development of AOB as a potential therapeutic for atopic diseases.GRAPHICAL ABSTRACTCreated with BioRender.comCompeting Interest StatementThe authors were employed by AOBiome Therapeutics at the time of this study; AOBiome Therapeutics is currently investigating the clinical use of AOB for treatment of atopic dermatitis.View Full Text