A Critical Role for SOCS3 in Innate Resistance to Toxoplasma gondii
| Autor: | David A. Christian, Christopher A. Hunter, Michael J. May, Carolyn M. Gray, Beth Gregg, Ryan J. Whitmarsh, Peter J. Murray |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Male
Cancer Research medicine.medical_treatment Suppressor of Cytokine Signaling Proteins Biology Microbiology Cell Line 03 medical and health sciences Mice 0302 clinical medicine Immune system Interferon Immunity Virology Immunology and Microbiology(all) medicine Animals Humans SOCS3 Interleukin 6 Molecular Biology Cells Cultured 030304 developmental biology Mice Knockout 0303 health sciences Interleukin-6 Macrophages Toxoplasma gondii biology.organism_classification Interleukin-12 Immunity Innate 3. Good health Cell biology Mice Inbred C57BL Cytokine Suppressor of Cytokine Signaling 3 Protein Immunology biology.protein Parasitology Female Signal transduction Toxoplasma Toxoplasmosis 030215 immunology medicine.drug Signal Transduction |
| Zdroj: | Cell Host & Microbe. (3):224-236 |
| ISSN: | 1931-3128 |
| DOI: | 10.1016/j.chom.2011.07.009 |
| Popis: | SummaryThe innate and adaptive immune responses that confer resistance to the intracellular pathogen Toxoplasma gondii critically depend on IL-12 production, which drives interferon-γ (IFN-γ) expression. Certain cytokines can activate STAT3 and limit IL-12 production to prevent infection-associated immune pathology, but T. gondii also directly activates STAT3 to evade host immunity. We show that suppressor of cytokine signaling molecule 3 (SOCS3), a target of STAT3 that limits signaling by the pleiotropic cytokine IL-6, is upregulated in response to infection but is dispensable for the immune-inhibitory effects of T. gondii. Unexpectedly, mice with targeted deletion of SOCS3 in macrophages and neutrophils have reduced IL-12 responses and succumb to toxoplasmosis. Anti-IL-6 administration or IL-12 treatment blocked disease susceptibility, suggesting that in the absence of SOCS3, macrophages are hypersensitive to the anti-inflammatory properties of IL-6. Thus, SOCS3 has a critical role in suppressing IL-6 signals and promoting immune responses to control T. gondii infection. |
| Databáze: | OpenAIRE |
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