[HTML][HTML] iNKT Cell Production of GM-CSF Controls Mycobacterium tuberculosis

AC Rothchild, P Jayaraman, C Nunes-Alves… - PLoS …, 2014 - journals.plos.org
AC Rothchild, P Jayaraman, C Nunes-Alves, SM Behar
PLoS pathogens, 2014journals.plos.org
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 …
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.
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