Thus, in the absence of these parasites, our immune responses

have become ‘hyperactive’, resulting in an increase in the prevalence of immune dysregulatory illnesses in the developed world. Future studies will show whether we can use hookworms, or preferably molecules derived from them, to correct this imbalance. Indeed, if vaccines and other control measures aimed at reducing the prevalence of hookworm (and other neglected tropical diseases) are implemented en masse, the resulting effect on the prevalence of autoimmunity and allergy in these countries is of potential concern. Our hookworm research is funded by the National Health and Medical Research Council of Australia (NHMRC), the Australian Research Council, The Broad Foundation and Sabin Vaccine Institute/Bill and Melinda selleck chemicals llc Gates Foundation. AL is the recipient of an NHMRC senior research fellowship. “
“FDA, Center for Food Safety and Applied Nutrition, Laurel, MD, USA Immaturity of gut-associated immunity may contribute to pediatric mortality associated with enteric infections. A murine model to parallel infantile enteric disease was used to determine the effects of probiotic, Lactobacillus acidophilus (La), selleck monoclonal humanized antibody prebiotic, inulin, or both (synbiotic, syn) on pathogen-induced inflammatory responses, NF-κB, and Smad 7 signaling. Newborn

mice were inoculated bi-weekly for 4 weeks with La, inulin, or syn BCKDHB and

challenged with Citrobacter rodentium (Cr) at 5 weeks. Mouse intestinal epithelial cells (CMT93) were exposed to Cr to determine temporal alterations in NF-Kappa B and Smad 7 levels. Mice with pretreatment of La, inulin, and syn show reduced intestinal inflammation following Cr infection compared with controls, which is associated with significantly reduced bacterial colonization in La, inulin, and syn animals. Our results further show that host defense against Cr infection correlated with enhanced colonic IL-10 and transforming growth factor-β expression and inhibition of NF-κB in syn-treated mice, whereas mice pretreated with syn, La, or inulin had attenuation of Cr-induced Smad 7 expression. There was a temporal Smad 7 and NF-κB intracellular accumulation post-Cr infection and post-tumor necrosis factor stimulation in CMT93 cells. These results, therefore, suggest that probiotic, La, prebiotic inulin, or synbiotic may promote host-protective immunity and attenuate Cr-induced intestinal inflammation through mechanisms affecting NF-κB and Smad 7 signaling. In the last two decades, diarrheal illnesses have accounted for approximately 4.6 million deaths of 1 billion episodes of diarrhea globally in children younger than 5 years (Snyder & Merson, 1982; Institute for World Health, 2010, http://www.oneworldhealth.org/diarrheal_disease).