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Tyk2-dependent bystander activation of conventional and nonconventional Th1 cell subsets contributes to innate host defense against Listeria monocytogenes infection.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 May 15; Vol. 192 (10), pp. 4739-47. Date of Electronic Publication: 2014 Apr 11. - Publication Year :
- 2014
-
Abstract
- IL-12, which is produced in response to intracellular bacteria, such as Listeria monocytogenes, promotes the development of pathogen-specific Th1 cells that play an important role in host defense. However, it has also been known that CD44(high) memory-phenotype CD4 T cells with Th1 functions naturally occur in naive mice, and that lymphopenia-induced proliferation of naive CD4 T cells generates memory-phenotype CD4 T cells with Th1 functions, although their differentiation mechanism and contribution to host defense are unclear. In this study, we analyzed the development and the functions of the different subsets of Th1 cells by using mice lacking tyrosine kinase 2 (Tyk2), a member of the Janus kinase family critically involved in IL-12 signaling. In contrast with the case of conventional Ag-specific Th1 cells, the development of naturally occurring Th1 cells was not impaired in Tyk2-deficient mice. In addition, Th1 cells were normally generated from Tyk2-deficient naive CD4 T cells via lymphopenia-induced proliferation. Nevertheless, all these Th1 subsets, including conventional Ag-induced Th1 cells, produced IFN-γ in response to IL-12 in a Tyk2-dependent manner. Importantly, such Tyk2-dependent bystander IFN-γ production of any Th1 subsets conferred early protection against L. monocytogenes infection. Thus, Tyk2-mediated IL-12 signaling is differentially required for the development of different Th1 cell subsets but similarly induces their bystander IFN-γ production, which contributes to innate host defense against infection with intracellular bacteria.
- Subjects :
- Animals
Antigens, Bacterial genetics
Antigens, Bacterial immunology
Bystander Effect genetics
Interferon-gamma genetics
Interferon-gamma immunology
Interleukin-12 genetics
Interleukin-12 immunology
Listeriosis genetics
Listeriosis pathology
Mice
Mice, Knockout
Signal Transduction genetics
Signal Transduction immunology
TYK2 Kinase genetics
Th1 Cells pathology
Bystander Effect immunology
Immunity, Innate
Listeria monocytogenes immunology
Listeriosis immunology
TYK2 Kinase immunology
Th1 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 192
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 24729620
- Full Text :
- https://doi.org/10.4049/jimmunol.1303067