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iNKT cell production of GM-CSF controls Mycobacterium tuberculosis

Rothchild, Alissa C.
Jayaraman, Pushpa
Nunes-Alves, Claudio
Behar, Samuel M
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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.

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PLoS Pathog. 2014 Jan;10(1):e1003805. doi: 10.1371/journal.ppat.1003805. Link to article on publisher's site

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DOI
10.1371/journal.ppat.1003805
PubMed ID
24391492
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© 2014 Rothchild et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.