Project description:Mouse infection with the tapeworm Hymenolepis diminuta leads to a less severe DNBS-colitis. Increased Th2 and regulatory cytokine production in the spleen is a hallmark of Hymenolepis diminuta infection, therefore we hypothesized that given this microenvironment, splenic adaptive cells acquire an anti-inflammatory phenotype. We tested the ability of putative splenic regulatory B cells generated by Hymenolepis diminuta infection to down-regulate intestinal inflammation. We found that unlike splenic B cells from uninfected mice, splenic B cells from Hymenolepis diminuta -infected animals ameliorated chemically-induced colitis.
Project description:Mouse infection with the tapeworm Hymenolepis diminuta leads to a less severe DNBS-colitis. Increased Th2 and regulatory cytokine production in the spleen is a hallmark of Hymenolepis diminuta infection, therefore we hypothesized that given this microenvironment, splenic adaptive cells acquire an anti-inflammatory phenotype. We tested the ability of putative splenic regulatory B cells generated by Hymenolepis diminuta infection to down-regulate intestinal inflammation. We found that unlike splenic B cells from uninfected mice, splenic B cells from Hymenolepis diminuta -infected animals ameliorated chemically-induced colitis. Splenic B cells were magnetically isolated and also purified by cell sorting from 7 days-infected animals and B cells from uninfected animals were used as control.
Project description:We tested the ability of rat worm Hymenolepis diminuta parasite crude antigens (HdAg) to induce a regulatory-associated program in bone-marrow derived macrophages (BMMs). Also, we compared gene expression profile of BMMs exposed to HdAg with those exposed to IL-4 which elicits a well-known alternative program.
Project description:Hymenolepis spp. (H. diminuta, H. nana and H. microstoma) are rodent-hosted tapeworms (Platyhelminthes: Cestoda) that have been used as laboratory and teaching models since the 1950s, and consequently much of our understanding of the basic physiology, biochemistry and anatomy of tapeworms in general stems from research using these species. As representatives of the order Cyclophyllidea, they are closely related to species with significant medical and economic importance such as Taenia and Echinococcus spp., but unlike these may be maintained in vivo using only laboratory mice and flour beetles (n.b. Echinoccous spp. are hosted by foxes and Taenia spp. are hosted by pigs or cows). This effort brings a classical laboratory model into the genomic age, allowing researchers in silico access to its genome and expressed gene transcripts and thereby greatly expediting research directed at understanding the genetic basis of tapeworm biology.
Project description:Recruited blood monocytes contribute to the establishment, perpetuation and resolution of tissue inflammation. Specifically, in the inflamed intestine, monocyte ablation was shown to ameliorate colitis scores in preclinical animal models. However, the majority of intestinal macrophages that seed the healthy gut are also monocyte-derived. Monocyte ablation aimed to curb inflammation would therefore likely interfere with intestinal homeostasis. Here, we used a TLR2 trans-membrane peptide which blocks TLR2 dimerization that is critical for TLR2 /1 and TLR2 / 6 heterodimer signaling to blunt inflammation in a murine colitis model. We show that while the TLR2 peptide treatment ameliorated colitis, it allowed recruited monocytes to give rise to macrophages that lack the detrimental pro-inflammatory gene signature and reduced potentially damaging neutrophils infiltrates. Finally, we demonstrate TLR blocking activity of the peptide on in vitro cultured human monocyte-derived macrophages. Collectively, we provide a significantly improved anti-inflammatory TLR2 peptide and critical insights in its mechanism of action towards future potential use in the clinic.
Project description:Transcriptional profiling of splenic lymphocytes derived from vaccinated mice, and ex-vivo exposed to M.tb.-infected macrophages in culture. Splenocytes from mice innoculated with Mycobacterium bovis BCG Pasteur (PAS), or M. bovis BCG Copenhagen (SSI), or heat killed BCG SSI (HK), or uninfected control, were ex vivo co-cultured with mouse bone marrow macrophages previously infected with M. tb.
