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TitleiNKT cell production of GM-CSF controls Mycobacterium tuberculosis
Author(s)Rothchild, Alissa C.
Jayaraman, Pushpa
Alves, Cláudio
Behar, Samuel M.
Granulocyte-Macrophage Colony-Stimulating Factor
Macrophages, Peritoneal
Mice, Knockout
Mycobacterium tuberculosis
Natural Killer T-Cells
Lymphocyte Activation
Issue dateJan-2014
PublisherPublic Library of Science (PLOS)
JournalPLoS Pathogens
CitationRothchild, A. C., Jayaraman, P., Nunes-Alves, C., & Behar, S. M. (2014). iNKT cell production of GM-CSF controls Mycobacterium tuberculosis. PLoS pathogens, 10(1), e1003805.
Abstract(s)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.
Publisher version
AccessRestricted access (UMinho)
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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