title: Pathogen-specific loss of host resistance in mice lacking the IFN-gamma-inducible gene IGTP.
abstract: Interferon-gamma (IFN-gamma) is critical for defense against pathogens, but the molecules that mediate its antimicrobial responses are largely unknown. IGTP is the prototype for a family of IFN-gamma-regulated genes that encode 48-kDa GTP-binding proteins that localize to the endoplasmic reticulum. We have generated IGTP-deficient mice and found that, despite normal immune cell development and normal clearance of Listeria monocytogenes and cytomegalovirus infections, the mice displayed a profound loss of host resistance to acute infections of the protozoan parasite Toxoplasma gondii. By contrast, IFN-gamma receptor-deficient mice have increased susceptibility to all three pathogens. Thus, IGTP defines an IFN-gamma-regulated pathway with a specialized role in antimicrobial resistance.
authors.affiliation: Advanced BioScience Laboratories Basic Research Program, National Cancer Institute/Frederick Cancer Research and Development Center (NCI/FCRDC), Frederick, MD 21702, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Taylor
authors.forename: C M
authors.initials: CM
authors.lastname: Collazo
authors.forename: G S
authors.initials: GS
authors.lastname: Yap
authors.forename: K
authors.initials: K
authors.lastname: Nguyen
authors.forename: T A
authors.initials: TA
authors.lastname: Gregorio
authors.forename: L S
authors.initials: LS
authors.lastname: Taylor
authors.forename: B
authors.initials: B
authors.lastname: Eagleson
authors.forename: L
authors.initials: L
authors.lastname: Secrest
authors.forename: E A
authors.initials: EA
authors.lastname: Southon
authors.forename: S W
authors.initials: SW
authors.lastname: Reid
authors.forename: L
authors.initials: L
authors.lastname: Tessarollo
authors.forename: M
authors.initials: M
authors.lastname: Bray
authors.forename: D W
authors.initials: DW
authors.lastname: McVicar
authors.forename: K L
authors.initials: KL
authors.lastname: Komschlies
authors.forename: H A
authors.initials: HA
authors.lastname: Young
authors.forename: C A
authors.initials: CA
authors.lastname: Biron
authors.forename: A
authors.initials: A
authors.lastname: Sher
authors.forename: G F
authors.initials: GF
authors.lastname: Vande Woude
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000382:microbiology / Q000469:parasitology; D003587:Cytomegalovirus / Q000472:pathogenicity; D005260:Female; D020558:GTP Phosphohydrolases / Q000172:deficiency / Q000235:genetics*; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D007239:Infections / Q000382:microbiology* / Q000401:mortality / Q000469:parasitology; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology*; D008089:Listeria monocytogenes / Q000472:pathogenicity; D008099:Liver / Q000378:metabolism / Q000382:microbiology / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000378:metabolism / Q000382:microbiology / Q000469:parasitology; D015996:Survival Rate; D014122:Toxoplasma / Q000472:pathogenicity
chemical_list: D012333:RNA, Messenger; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D020558:GTP Phosphohydrolases; C101131:Igtp protein, mouse