Sep 09, 2011
from 12:00 PM to 01:00 PM
|Where||G100 Bondurant Hall|
|Contact Name||Tamea Ricardson-Love|
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Function of the Interferon-Inducible Immunity-Related GTPases in the Innate Immune Response to Toxoplasma Gondii Infection
It is becoming increasingly clear that cell-autonomous resistance mechanisms exist that tend to counteract the replication and survival of intracellular pathogens. These resistance programs are not restricted to cells of the classical immune system like B-cells, T-cells or macrophages but are potentially active in every body cell. Such mechanisms are normally latent in uninfected or unstimulated cells but are activated by cytokines and especially interferons. Interferons are produced upon infection and are subdivided into type I and type II interferons. Type I interferons are secreted by virus infected cells while secretion of type II interferon, also called interferon-γ (IFN-γ), is restricted to T-cells, NK-cells and macrophages. The two classes of interferons induce an extraordinarily complex cellular response regulating the expression of several hundred genes.
An intracellular way of life can protect pathogens from antibodies, but hosts can deploy other specialized defense mechanisms against such pathogens. Toxoplasma gondii, is an intracellular protozoal pathogen of mammals and birds, and commonly infects humans. Mice exploit a specialized intracellular resistance system, the IFN-γ inducible immunity-related GTPases (IRG proteins, also known as p47 GTPases), for defense against T. gondii. IRG proteins accumulate rapidly on the membrane surrounding intracellular parasites. Shortly after, this membrane ruptures and the parasite dies. This process is followed by the necrotic death of the host cell. IRG proteins are GTPases, enzymes that release chemical energy by breaking down guanosine trisphosphate (GTP) in the cell. Probably, they can convert released chemical energy into the mechanical force that damages the vacuole membrane.
Selected Key Publications:
Christoph Rohde, Julia P. Hunn, Andreas Meinhardt, Jonathan C. Howard (2011) The conserved Immunity-related GTPase IRGC/Irgc is expressed in haploid spermatids. (Manuscript awaiting submission)
Liesenfeld, O, Parvanova, IA, Zerrahn, J, Han, SJ, Heinrich, F, Munoz, M, Kaiser, F, Aebischer, T, Buch,, T, Waisman, A, Reichmann, G, Utermöhlen, O, von Stebut, E, Bogdan, C, Specht, S, Saeftel, M, Hoerauf, A, Mota, M, Könen-Waisman, S, Kaufmann, SHE, Howard, JC (2011) Irga6/IIGP contributes to in vivo resistance against Toxoplasma gondii infection but not to resistance against other intracellular pathogens including Plasmodium berghei. PLoS One, in press
Nikolaus Pawlowski, Aliaksandr Khaminets, Julia P. Hunn, Natasa Papic, Andreas Schmid, Revathy C. Uthaiah, Rita Lange, Gaby Vopper, Sascha Martens, Eva Wolf, Jonathan C. Howard (2011) The Activation Mechanism of Irga6, an Interferon-Inducible GTPase Contributing to Mouse Resistance against Toxoplasma gondii. BMC Biology 9:7.