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Mice deficient in LRG-47 display enhanced susceptibility to Trypanosoma cruzi infection associated with defective hemopoiesis and intracellular control of parasite growth
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 175(12)
- Publication Year :
- 2005
-
Abstract
- IFN-γ is known to be required for host control of intracellular Trypanosoma cruzi infection in mice, although the basis of its protective function is poorly understood. LRG-47 is an IFN-inducible p47GTPase that has been shown to regulate host resistance to intracellular pathogens. To investigate the possible role of LRG-47 in IFN-γ-dependent control of T. cruzi infection, LRG-47 knockout (KO) and wild-type (WT) mice were infected with the Y strain of this parasite, and host responses were analyzed. When assayed on day 12 after parasite inoculation, LRG-47 KO mice, in contrast to IFN-γ KO mice, controlled early parasitemia almost as effectively as WT animals. However, the infected LRG-47 KO mice displayed a rebound in parasite growth on day 15, and all succumbed to the infection by day 19. Additional analysis indicated that LRG-47-deficient mice exhibit unimpaired proinflammatory responses throughout the infection. Instead, reactivated disease in the KO animals was associated with severe splenic and thymic atrophy, anemia, and thrombocytopenia not observed in their WT counterparts. In addition, in vitro studies revealed that IFN-γ-stimulated LRG-47 KO macrophages display defective intracellular killing of amastigotes despite normal expression of TNF and NO synthetase type 2 and that both NO synthetase type 2 and LRG-47 are required for optimum IFN-γ-dependent restriction of parasite growth. Together, these data establish that LRG-47 can influence pathogen control by simultaneously regulating macrophage-microbicidal activity and hemopoietic function.
- Subjects :
- Trypanosoma cruzi
Immunology
Nitric Oxide Synthase Type II
Parasitemia
Biology
Proinflammatory cytokine
Host-Parasite Interactions
Interferon-gamma
Mice
GTP-Binding Proteins
medicine
Immunology and Allergy
Animals
Chagas Disease
Amastigote
Pathogen
Mice, Knockout
Intracellular parasite
Macrophages
medicine.disease
biology.organism_classification
Hematopoiesis
Tumor necrosis factor alpha
Disease Susceptibility
Intracellular
Subjects
Details
- ISSN :
- 00221767
- Volume :
- 175
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....9ae811edc623db3d55a0df9d901213a7