Titolo della tesi: Symbiotic, opportunistic, and probiotic microbes: new advances in understanding their interaction with immune system
In this thesis we analysed the impact of Saccharomyces cerevisiae, Acinetobacter baumannii, and Lactobacillus reuteri on human immune system.
S. cerevisiae is a yeast harboring the human gastrointestinal tract, and the interaction with human blood dendritic cells (DCs) was never been investigated. We found that conventional DC (cDCs) and plasmacytoid DCs (pDCs) sense S. cerevisiae and that cDCs induce IL-6 and IL-17 production, while pDCs IFN-α and IL-10 , with pro- and anti-inflammatory properties, respectively. These results could have relevant implication in health and diseases associated to microbiota dysbiosis.
A. baumannii is a nosocomial bacteria promoting pathology in immunocompromised hosts. We analysed for the first time the response of human innate immune cells to A. baumannii ATCC19606T (low virulence) and ACICU (high virulence). We found that macrophages promote killing of both bacterial strains, monocytes kill preferentially ATCC19606T, DCs and monocytes produce cytokines. Importantly, ACICU induces lower expression of two cytokines that have been associated to protection against A. baumannii: IL-10, IFN-α. Thus, we identified mechanisms potentially related to the high virulence of the multidrug-resistant strain.
L. reuteri is a probiotic with beneficial properties. We studied the effect of L. reuteri in children with autism spectrum disorder (ASD), characterized by social problems and gastrointestinal dysbiosis. Since we previously demonstrated a pro-social effect of L. reuteri supplementation, we analysed the effects of probiotic on immune system and microbiota. We observed an increase of fecal F.prausnitzii and E. rectale, with anti-inflammatory properties, and a decrease of plasmatic soluble CD40L, with pro-inflammatory properties, in probiotic-treated ASD children. These results indicate an anti-inflammatory role of probiotic L. reuteri in ASD children.
Overall, we uncovered new mechanisms involved in the regulation of host/microbe interaction, with potential implication in the response to pathogenic infections, prevention of excessive inflammation, and exploitation of beneficial effect of microbiota and probiotics.