Pathogen-specific loss of host resistance in mice lacking the IFN-gamma-inducible gene IGTP.
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.
Taylor
G A
GA
Advanced BioScience Laboratories Basic Research Program, National Cancer Institute/Frederick Cancer Research and Development Center (NCI/FCRDC), Frederick, MD 21702, USA.
Collazo
C M
CM
Yap
G S
GS
Nguyen
K
K
Gregorio
T A
TA
Taylor
L S
LS
Eagleson
B
B
Secrest
L
L
Southon
E A
EA
Reid
S W
SW
Tessarollo
L
L
Bray
M
M
McVicar
D W
DW
Komschlies
K L
KL
Young
H A
HA
Biron
C A
CA
Sher
A
A
Vande Woude
G F
GF
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
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