STAT1 Is Essential for Antimicrobial Effector Function but Dispensable for Gamma Interferon Production during Toxoplasma gondii Infection
AUTOR(ES)
Gavrilescu, L. Cristina
FONTE
American Society for Microbiology
RESUMO
The opportunistic protozoan Toxoplasma gondii is a prototypic Th1-inducing pathogen inducing strong gamma interferon (IFN-γ) cytokine responses that are required to survive infection. Intracellular signaling intermediate STAT1 mediates many effects of IFN-γ and is implicated in activation of T-bet, a master regulator of Th1 differentiation. Here, we show that T. gondii-infected STAT1-null mice fail to upregulate the IFN-γ-dependent effector molecules inducible nitric oxide synthase (iNOS), IGTP, and LRG-47, which are required for mice to survive infection. Both T-bet and interleukin-12 receptor β2 (IL-12Rβ2) failed to undergo normal upregulation in response to T. gondii. Development of IFN-γ-producing CD4+ and CD8+ T lymphocytes was severely curtailed in the absence of STAT1, but a substantial level of STAT1-independent non-T-cell-derived IFN-γ was induced. Absence of STAT1 also resulted in increased IL-4, Arg1, Ym1, and Fizz1, markers of Th2 differentiation and alternative macrophage activation. Together, the results show that T. gondii induces STAT1-dependent T-lymphocyte and STAT1-independent non-T-cell IFN-γ production, but that effector functions of this type 1 cytokine cannot operate in the absence of STAT1, resulting in extreme susceptibility to acute infection.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=356043Documentos Relacionados
- The Linker Domain of Stat1 Is Required for Gamma Interferon-Driven Transcription
- The Function of Gamma Interferon-Inducible GTP-Binding Protein IGTP in Host Resistance to Toxoplasma gondii Is Stat1 Dependent and Requires Expression in Both Hematopoietic and Nonhematopoietic Cellular Compartments
- Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma.
- Replication of Toxoplasma gondii, but Not Trypanosoma cruzi, Is Regulated in Human Fibroblasts Activated with Gamma Interferon: Requirement of a Functional JAK/STAT Pathway
- Selective STAT Protein Degradation Induced by Paramyxoviruses Requires both STAT1 and STAT2 but Is Independent of Alpha/Beta Interferon Signal Transduction