Friday Science Review: December 16, 2011
December 16, 2011
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Homeostasis in the Gut, Plasma Cells on Patrol
University of Toronto ♦ McGill University ♦ University of Bern ♦ Memorial University of Newfoundland
Published in Nature, December 11, 2011
The intestine is the largest mucosal surface in the body and is exposed to a diversity of microbes. This microbial life is healthy, although the immune system must still keep bacterial population sizes in check. One mechanism by which this is achieved is through the differentiation of B cells to plasma cells, which in turn secrete the immunoglobulin IgA. New findings indicate that plasma cells have additional roles that keep microbiota at bay. Researchers found that plasma cells secrete tumor-necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), both of which exert antimicrobial activity. Microbial co-stimulation is pre-requisite for plasma cell multi-functionality. In order to investigate the effects that TNF-α and iNOS have on regulating flora in the gut, researchers used a double knockout mouse model. Removal of the two mediators led to a change in the composition of intestinal flora and a reduction in secretion of IgA from plasma cells.
VSV 2.0: IL-15 Engineered
McMaster University ♦ Published in Cancer Gene Therapy (npg), December 9, 2011
A popular approach to the development of oncolytic viruses for cancer therapy has been the use of the single-stranded RNA virus known vesicular stomatitis virus (VSV). This particular virus has a hypersensitivity to the protein type I interferon (IFN). Upon exposure to a virus the body releases IFN in attempt to prevent infection. The beauty of VSV is that while normal healthy cells are highly sensitive to IFN, tumour cells remain hyporesponsive. Systemic administration of VSV has little to no effect on normal cells as the virus cannot replicate within them. However, because they fail to respond to IFN, cancer cells remain susceptible to VSV infection, VSV replication, and eventually cell lysis. While VSV alone has been shown to be effective in preclinical models, long-term survival is not greatly increased.
Researchers at McMaster’s Centre for Gene Therapeutics have upped the anti with the development of a genetically engineered VSV that expresses an interleukin-15 (IL-15) transgene. IL-15 is a cytokine that has a critical role in adaptive immune responses to pathogenic entities. The group showed that injections of the IL-15 VSV in a mouse model of colon cancer led to strong localized expression of the cytokine in vivo. The new IL-15-rich microenvironment surrounding tumours increased the adaptive immune response targeted at tumour cells by recruiting and activating natural killer cells and T-cells. This novel virus has the two-fold effect of not only lysing cells, but enhancing anti-tumoral T-cell response. Mice receiving injections exhibited better survival overall.