Extensive characterization of IFN-induced GTPases mGBP1 to mGBP10 involved in host defense.
IFN-gamma orchestrates a potent antimicrobial host response. However, the underlying molecular basis for this immunological defense system is largely unknown. In a systematic approach to identify IFN-gamma-regulated host effector molecules, a notable number of transcripts with consensus GTP-binding motives were obtained. Further extensive transcriptome and genome analyses identified five novel family members of murine guanylate-binding proteins (mGBPs) now designated mGBP6, 7, 8, 9, and 10. Moreover, in this study, all 10 mGBP members (mGBP1-10) were extensively characterized. mGBPs are selectively up-regulated in vitro by a set of proinflammatory cytokines and TLR agonists as well as in vivo after Listeria monocytogenes and Toxoplasma gondii infection. After IFN-gamma stimulation, mGBP1, 2, 3, 6, 7, and 9 are associated with intracellular Toxoplasma parasites and, interestingly, virulent Toxoplasma interfere with mGBP recruitment. Taken together, mGBPs comprise an important set of host defense molecules.
Degrandi
Daniel
D
Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University, Dusseldorf, Germany.
Konermann
Carolin
C
Beuter-Gunia
Cornelia
C
Kresse
Alexandra
A
Würthner
Jan
J
Kurig
Stefanie
S
Beer
Sandra
S
Pfeffer
Klaus
K
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004195:Disease Models, Animal; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000494:pharmacology*; D008089:Listeria monocytogenes / Q000276:immunology / Q000302:isolation & purification; D008088:Listeriosis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D014122:Toxoplasma / Q000276:immunology / Q000302:isolation & purification; D014124:Toxoplasmosis, Animal / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
C490288:Gbp2b protein, mouse; D007371:Interferon-gamma; D019204:GTP-Binding Proteins; C526194:Gbp6 protein, mouse; C526195:Gbp8 protein, mouse