University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Department of Microbiology and Physiological Systems
Publication Date
2014-01-02
Document Type
Article
Disciplines
Bacteria | Bacterial Infections and Mycoses | Immunopathology | Pathogenic Microbiology
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 IFNgamma 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 IFNgamma. 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.
Rights and Permissions
© 2014 Rothchild et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
10.1371/journal.ppat.1003805
Source
PLoS Pathog. 2014 Jan;10(1):e1003805. doi: 10.1371/journal.ppat.1003805. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
PLoS pathogens
PubMed ID
24391492
Repository Citation
Rothchild AC, Jayaraman P, Nunes-Alves C, Behar SM. (2014). iNKT cell production of GM-CSF controls Mycobacterium tuberculosis. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1371/journal.ppat.1003805. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/441
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Bacteria Commons, Bacterial Infections and Mycoses Commons, Immunopathology Commons, Pathogenic Microbiology Commons