Toll-like Rezeptoren: Ziele der herpesviralen Immun-Evasion?
Zusammenfassung der Projektergebnisse
The human body's defense against invading pathogens such as viruses and bacteria is mediated by two components of the immune system: innate and adaptive immunity. Both components recognize microorganisms as "non-self" and efficiently lead to their elimination. Upon infection of the host by invading pathogens the innate immune system constitutes the first line of defense, and members of a protein family named Tolllike receptors are essential players in it. They specifically recognize "patterns" of bacteria or viruses and set the infected cell and surrounding cells into an alert state by inducing the production of messenger substances. In order to recognize the intruders, the Toll-like receptors need to travel to distinct locations within the infected cell, where they meet and bind the "patterns" of pathogens such as nucleic acid or proteins. How the traveling of Toll-like receptors is initiated is largely unknown. With this two year project I significantly contributed to the understanding of trafficking of intracellularly located nucleic-acid sensing TLRs by identifying the previously uncharacterized membrane protein UNC93B as an interaction partner of these TLRs. We could further show that these TLRs need the UNC93B protein to travel to the location where they meet invading pathogens, which is the prerequisite for their efficient elimination. These findings may help design strategies to counteract the maneuvers used by pathogens to escape immune destruction.
Projektbezogene Publikationen (Auswahl)
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"Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae". Journal of General Virology (2006), 87 (Pt5), pp. 1047-1074
M. M. Brinkmann and T. F. Schulz
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"The Kaposi's Sarcoma-Associated Herpesvirus LANA-1 interacts with the short variant of BRD4 and releases cells from a BRD4- and BRD2/RING3- induced G1 cell cycle arrest". Journal of Virology (2006), 80 (21), pp. 10772-86
M. Ottinger, T. Christalla, K. Nathan, M. M. Brinkmann, A. Viejo-Borbolla, and T. F. Schulz
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"Functional Characterization of the M-type K15 Encoded Membrane Protein of Kaposi's Sarcoma Herpesvirus". Journal of General Virology (2007), 88 (6), pp. 1698-1707
L. Wang, M. M. Brinkmann, M. Pietrek, M. Ottinger, O. Dittrich-Breiholz, M. Kracht and T. F. Schulz
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"Modulation of host gene expression by the K15 protein of Kaposi's sarcomaassociated herpesvirus". Journal of Virology (2007), 81 (1), pp. 42-58
M. M. Brinkmann, M. Pietrek, O. Dittrich-Breiholz, M. Kracht, and T. F. Schulz
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"The interaction between the ER membrane protein UNC93B and TLRs 3, 7 and 9 is crucial for TLR signaling". Journal of Cell Biology (2007), Vol. 177, (2), pp. 265-275
M. M. Brinkmann, E. Spooner, K. Hoebe, B. Beutler, H. L. Ploegh & Y.-M. Kim
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"TLRs 'bent' into shape". Nature Immunology (2007), 8 (7): pp. 675-7
Y.-M. Kim, M. M. Brinkmann and H. L. Ploegh
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"UNC93B controls intracellular trafficking of nucleotide-sensing toll-like receptors". Nature (2008), Vol. 452, pp. 234-238
Y.-M. Kim, M. M. Brinkmann, M.-E. Paquet & H. L. Ploegh
