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iNKT Cell Production of GM-CSF Controls Mycobacterium tuberculosis.

Authors :
Rothchild, Alissa C.
Jayaraman, Pushpa
Nunes-Alves, Cláudio
Behar, Samuel M.
Source :
PLoS Pathogens; Jan2014, Vol. 10 Issue 1, p1-13, 13p
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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15537366
Volume :
10
Issue :
1
Database :
Complementary Index
Journal :
PLoS Pathogens
Publication Type :
Academic Journal
Accession number :
94233253
Full Text :
https://doi.org/10.1371/journal.ppat.1003805