Because our lab was shut down by the NIAID administration on APril 1st, 2013, we focused on three projects that had some possibility of completion. We did not manage to finish two of these project, but will continue them through collaborations with other scientists on and off campus. 1) (completed) analysis of the effect of antibiotics on gene expression in intestinal epithelial cells, and changes in microbiota. 2) (not completed) analysis of the stimulatory effect of P gingivalis (PG) on dendritic cells: we compared the stimulatory capacity of PG with that of E coli, and found that PG are almost entirely non-stimulatory. For example, it takes 1000 times more PG LPS than E coli LPS to stimulate dendritic cells. Further, PG has the capacity to degrade several key immune cyctokines made by dendritic cells and/or T cells. 3) (not completed) analysis of the effect of GATA4: GATA 4 is a transcription factor highly expressed by the epithelial cells of the jejunum. In mice carrying a targeted deletion in jejunal GATA4, the jejunal epithelial cells upregulate a network of immune genes. To determine whether the immune upregulation is a direct effect of the loss of GATA4, or an indirect effect because of GATA4-induced changes in the intestinal flora, we took two approaches. First we generated germ-free GATA4KO mice. Second we used siRNA to downregulate GATA4 in the intestinal cell line, MODE-K. The germ free mice are now sitting, waiting for a collaborator to collect their tissues, as we are not being allowed to spend our budget to do this. The cell line revealed that at least three immune genes are upregulated, in the absence of bacteria, when GATA4 is downregulated by siRNA.

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Fuchs, E J; Matzinger, P (2018) Does the Danger model shed any light on central tolerance?: A response to Al-Yassin. Scand J Immunol 88:e12660
Abdi, Kaveh; Chen, Tsute; Klein, Brian A et al. (2017) Mechanisms by which Porphyromonas gingivalis evades innate immunity. PLoS One 12:e0182164
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Matzinger, Polly (2012) The evolution of the danger theory. Interview by Lauren Constable, Commissioning Editor. Expert Rev Clin Immunol 8:311-7
Abdi, Kaveh; Singh, Nevil J; Matzinger, Polly (2012) Lipopolysaccharide-activated dendritic cells: ""exhausted"" or alert and waiting? J Immunol 188:5981-9
Matzinger, Polly; Kamala, Tirumalai (2011) Tissue-based class control: the other side of tolerance. Nat Rev Immunol 11:221-30
Gonzaga, Rosemary; Matzinger, Polly; Perez-Diez, Ainhoa (2011) Resident peritoneal NK cells. J Immunol 187:6235-42

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