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Network topologies and dynamics leading to endotoxin tolerance and priming in innate immune cells


, : Network topologies and dynamics leading to endotoxin tolerance and priming in innate immune cells. Plos Computational Biology 8(5): E1002526-E1002526

The innate immune system, acting as the first line of host defense, senses and adapts to foreign challenges through complex intracellular and intercellular signaling networks. Endotoxin tolerance and priming elicited by macrophages are classic examples of the complex adaptation of innate immune cells. Upon repetitive exposures to different doses of bacterial endotoxin (lipopolysaccharide) or other stimulants, macrophages show either suppressed or augmented inflammatory responses compared to a single exposure to the stimulant. Endotoxin tolerance and priming are critically involved in both immune homeostasis and the pathogenesis of diverse inflammatory diseases. However, the underlying molecular mechanisms are not well understood. By means of a computational search through the parameter space of a coarse-grained three-node network with a two-stage Metropolis sampling approach, we enumerated all the network topologies that can generate priming or tolerance. We discovered three major mechanisms for priming (pathway synergy, suppressor deactivation, activator induction) and one for tolerance (inhibitor persistence). These results not only explain existing experimental observations, but also reveal intriguing test scenarios for future experimental studies to clarify mechanisms of endotoxin priming and tolerance.

US$19.90

PMID: 22615556

DOI: 10.1371/journal.pcbi.1002526


Other references

Kimura, T.; Ozawa, T., 2002: A new cetothere Cetacea Mysticeti from the Early Miocene of Japan. Two well-preserved specimens of a "cetothere" from the Lower Miocene Awa and Mizunami Groups, Japan, are described as Isanacetus laticephalus, gen. et sp. nov. It is distinguished by the following combination of characters: fossa for the...

Jung, R.; Tümmler, J.; Will, I., 2016: Regenerative thin-disk amplifier for 300 mJ pulse energy. A regenerative amplifier based on thin-disk technology has been upgraded and optimized. Within a CPA laser system chirped 1 ns pulses are amplified to more than 300 mJ pulse energy. In addition to the high pulse energy the amplifier shows a very g...

Yee, J.; Petsikas, D.; Ricci, M.A.; Guerraty, A., 1990: General surgical procedures after heart transplantation. Seventy-eight cardiac transplantations were performed between July 1982 and March 1989. The perioperative death rate was 10%. Overall survival was 86%. Among the long-term survivors, 14 patients underwent 16 noncardiac surgical procedures. Seven o...

Katsuta, H.; Takaoka, T.; Oishi, Y.; Baba, T.; Chang, K.C., 1954: Cultivation of fibroblasts from chick embryo heart in the simplified replicate tissue culture. For the convenience of routine experiments on the cell growth, the replicate tissue culture method by Earle et al. was simplified in this study. Using this technique, various fundamental conditions for the cultivation of chick fibroblasts were stu...

Volden, Birger, 1996: Nitrogen and potassium fertilization of leys in northern Norway. II. Chemical and in vitro analyses of the forage. A series of field trials over a four year period with different rates and distributions of N and K fertilizer was carried out in timothy dominated leys. The crude protein (CP) content of grass DM at first cut (timothy at heading) increased from 11...

Lavelli, V., 2013: High-warranty traceability system in the poultry meat supply chain A medium-sized enterprise case study. The concept of food traceability can be traced back 5000 years to Egyptian society. Over the last decade, traceability has become recognized as an essential food safety and food quality tool. Food safety legislation and voluntary standards have de...

Maga, G.; Falchi, F.; Garbelli, A.; Belfiore, A.; Witvrouw, M.; Manetti, F.; Botta, M., 2008: Pharmacophore modeling and molecular docking led to the discovery of inhibitors of human immunodeficiency virus-1 replication targeting the human cellular aspartic acid-glutamic acid-alanine-aspartic acid box polypeptide 3. HIV-1 replication has been inhibited by using a compound able to target the human cellular cofactor DEAD-box ATPase DDX3, essential for HIV-1 RNA nuclear export. This compound, identified by means of a computational protocol based on pharmacophori...

Desai, P.M.; Pfeiffer, M.L.; Pohlmeier, M.M.; Raymond, J.B., 1996: Dual-stage process for manufacturing potato chips. Official Gazette of the United States Patent & Trademark Office Patents 1193(5): 3505, Dec 31

Suda, Y.; Kim, Y.; Nagata, K.; Shimoyama, T.; Kusumoto, S.; Tamura, T., 2002: Structure and function of Helicobacter pylori lipid A. Journal of Endotoxin Research 8(3): 166

Gillett, P.G., 1977: Immunologic control of fertility: search for a contraceptive vaccine. Clinical Obstetrics and Gynecology 20(3): 705-715