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iNKT cell production of GM-CSF controls Mycobacterium tuberculosis.
- Source :
-
PLoS pathogens [PLoS Pathog] 2014 Jan; Vol. 10 (1), pp. e1003805. Date of Electronic Publication: 2014 Jan 02. - Publication Year :
- 2014
-
Abstract
- Invariant natural killer T (iNKT) cells are activated during infection, but how they limit microbial growth is unknown in most cases. We investigated how iNKT cells suppress intracellular Mycobacterium tuberculosis (Mtb) replication. When co-cultured with infected macrophages, iNKT cell activation, as measured by CD25 upregulation and IFNγ production, was primarily driven by IL-12 and IL-18. In contrast, iNKT cell control of Mtb growth was CD1d-dependent, and did not require IL-12, IL-18, or IFNγ. This demonstrated that conventional activation markers did not correlate with iNKT cell effector function during Mtb infection. iNKT cell control of Mtb replication was also independent of TNF and cell-mediated cytotoxicity. By dissociating cytokine-driven activation and CD1d-restricted effector function, we uncovered a novel mediator of iNKT cell antimicrobial activity: GM-CSF. iNKT cells produced GM-CSF in vitro and in vivo in a CD1d-dependent manner during Mtb infection, and GM-CSF was both necessary and sufficient to control Mtb growth. Here, we have identified GM-CSF production as a novel iNKT cell antimicrobial effector function and uncovered a potential role for GM-CSF in T cell immunity against Mtb.
- Subjects :
- Animals
Granulocyte-Macrophage Colony-Stimulating Factor genetics
Granulocyte-Macrophage Colony-Stimulating Factor immunology
Interferon-gamma genetics
Interferon-gamma immunology
Interleukin-12 genetics
Interleukin-12 immunology
Interleukin-18 genetics
Interleukin-18 immunology
Macrophages, Peritoneal microbiology
Macrophages, Peritoneal pathology
Mice
Mice, Knockout
Natural Killer T-Cells pathology
Tuberculosis genetics
Tuberculosis pathology
Lymphocyte Activation
Macrophages, Peritoneal immunology
Mycobacterium tuberculosis immunology
Natural Killer T-Cells immunology
Tuberculosis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 24391492
- Full Text :
- https://doi.org/10.1371/journal.ppat.1003805