Michael Abt

Publications (2)6.39 Total impact

• Article: The intestinal microbiota in health and disease: the influence of microbial products on immune cell homeostasis.

  Michael C Abt, David Artis
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  ABSTRACT: A vast and diverse array of microbes colonizes the mammalian gastrointestinal tract. These microorganisms are integral in shaping the development and function of the immune system. Metagenomic sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from chronic inflammatory diseases, including inflammatory bowel disease and asthma. This review will discuss the mechanisms through which the innate immune system recognizes and responds to the intestinal microbiota as well as the effect of specific microbiota-derived signals on immune cell homeostasis. Recent studies in murine model systems have demonstrated that manipulation of the intestinal microbiota can alter mammalian immune cell homeostasis. Specific microbial signals have been identified that can impact immune cell function both within the intestinal tract and in peripheral tissues. These microbiota-derived signals can either have an immunoregulatory effect, creating an immune state that is refractory to inflammation, or conversely, act as an adjuvant, aiding in the propagation of an immune response. Associations between alterations in the microbiota and human disease implicate intestinal microbial signals in shaping immune responses. These signals are recognized by innate immune cells and influence the ability of these cells to modulate both the local and systemic immune response.
  Current opinion in gastroenterology 09/2009; 25(6):496-502. · 4.33 Impact Factor
• Article: Characterization of phenoloxidase activity in venom from the ectoparasitoid Nasonia vitripennis (Walker) (Hymenoptera: Pteromalidae).

  Michael Abt, David B Rivers
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  ABSTRACT: Crude venom isolated from the ectoparasitic wasp Nasonia vitripennis was found to possess phenoloxidase (PO) activity. Enzyme activity was detected by using a modified dot blot analysis approach in which venom samples were applied to nylon membranes and incubated with either L-DOPA or dopamine. Dot formation was most intense with dopamine as the substrate and no activators appeared to be necessary to evoke a melanization reaction. No melanization occurred when venom was incubated in Schneider's insect medium containing 10% fetal bovine serum or when using tyrosine as a substrate, but melanization did occur when larval or pupal plasma from the fly host, Sarcophaga bullata, was exposed to tyrosine. Only fly larval plasma induced an enzyme reaction with the Schneider's insect medium. The PO inhibitor phenylthiourea (PTU) and serine protease inhibitor phenylmethylsulfonylfluoride (PMSF) abolished PO activity in venom and host plasma samples, but glutathione (reduced) only inhibited venom PO. Elicitors of PO activity (sodium dodecyl sulfate and trypsin) had no or a modest effect (increase) on the ability of venom, or larval and pupal plasma to trigger melanization reactions. SDS-PAGE separation of crude venom followed by in-gel staining using L-DOPA as a substrate revealed two venom proteins with PO activity with estimated molecular weights of 68 and 160 kDa. In vitro assays using BTI-TN-5B1-4 cells were performed to determine the importance of venom PO in triggering cellular changes and evoking cell death. When cell monolayers were pre-treated with 10 mM PTU or PMSF prior to venom exposure, the cells were protected from the effects of venom intoxication as evidenced by no observable cellular morphological changes and over 90% cell viability by 24 h after venom treatment. Simultaneous addition of inhibitors with venom or lower concentrations of PMSF were less effective in affording protection. These observations collectively argue that wasp venom PO is unique from that of the fly hosts, and that the venom enzyme is critical in the intoxication pathway leading to cell death.
  Journal of Invertebrate Pathology 03/2007; 94(2):108-18. · 2.06 Impact Factor