(1) Differential Effects of Escherichia coli Nissle and Lactobacillus rhamnosus strain GG on Human Rotavirus Infection and B Cell Responses

(1)  Microbiota play a significant role in modulating host-pathogen interactions. We studied the role of gram-positive [Lactobacillus rhamnosus strain GG (LGG)] and gram-negative [Escherichia coli Nissle (EcN)] commensal bacteria on virulent human rotavirus (HRV) infection and immunity using neonatal gnotobiotic (Gn) piglets.  Gn piglets were colonized with EcN, LGG or EcN+LGG and challenged with virulent HRV. Mean peak virus shedding titers were significantly lower in EcN-colonized compared to LGG-colonized or uncolonized piglets. Coinciding with lower virus shedding, serum IFNα levels were significantly lower in EcN-colonized piglets compared to LGG-colonized or uncolonized piglets post-challenge. Reduced viral shedding titers were correlated with significantly reduced small intestinal and serum anti-HRV IgA responses in EcN-colonized compared to uncolonized piglets post-challenge. However the total IgA levels post-challenge in intestine and pre-challenge in serum were significantly higher in EcN-colonized than in LGG-colonized piglets. In vitro treatment of mononuclear cells (MNCs) with these probiotics demonstrated that EcN, but not LGG, induced IL6, IL10 and IgA, with the latter partially dependent on IL10. Exogenous addition of recombinant porcine IL10 and IL6 to MNCs co-cultured with LGG significantly enhanced IgA responses. Our results suggest that EcN and LGG differentially modulate rotavirus infection and B cell responses.