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Cell death of gamma interferon-stimulated human fibroblasts upon Toxoplasma gondii infection induces early parasite egress and limits parasite replication.
- Source :
-
Infection and immunity [Infect Immun] 2013 Dec; Vol. 81 (12), pp. 4341-9. Date of Electronic Publication: 2013 Sep 16. - Publication Year :
- 2013
-
Abstract
- The intracellular protozoan parasite Toxoplasma gondii is a major food-borne illness and opportunistic infection for the immunosuppressed. Resistance to Toxoplasma is dependent on gamma interferon (IFN-γ) activation of both hematopoietic and nonhematopoietic cells. Although IFN-γ-induced innate immunity in nonhematopoietic cells has been extensively studied in mice, it remains unclear what resistance mechanisms are relied on in nonhematopoietic human cells. Here, we report an IFN-γ-induced mechanism of resistance to Toxoplasma in primary human foreskin fibroblasts (HFFs) that does not depend on the deprivation of tryptophan or iron. In addition, infection is still controlled in HFFs deficient in the p65 guanylate binding proteins GBP1 or GBP2 and the autophagic protein ATG5. Resistance is coincident with host cell death that is not dependent on the necroptosis mediator RIPK3 or caspases and is correlated with early egress of the parasite before replication. This IFN-γ-induced cell death and early egress limits replication in HFFs and could promote clearance of the parasite by immune cells.
- Subjects :
- Autophagy-Related Protein 5
Cells, Cultured
Fibroblasts
GTP-Binding Proteins deficiency
GTP-Binding Proteins genetics
GTP-Binding Proteins immunology
Humans
Iron
Microtubule-Associated Proteins deficiency
Microtubule-Associated Proteins genetics
Microtubule-Associated Proteins immunology
RNA Interference
RNA, Small Interfering
Receptor-Interacting Protein Serine-Threonine Kinases metabolism
Tryptophan
Apoptosis immunology
Interferon-gamma metabolism
Toxoplasma immunology
Toxoplasmosis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5522
- Volume :
- 81
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 24042117
- Full Text :
- https://doi.org/10.1128/IAI.00416-13