Rothchild, Alissa ChenJayaraman, PushpaNunes-Alves, CláudioBehar, Samuel M.2014-03-112014Rothchild, Alissa C., Pushpa Jayaraman, Cláudio Nunes-Alves, and Samuel M. Behar. 2014. “iNKT Cell Production of GM-CSF Controls Mycobacterium tuberculosis.” PLoS Pathogens 10 (1): e1003805. doi:10.1371/journal.ppat.1003805. http://dx.doi.org/10.1371/journal.ppat.1003805.1553-7366http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879458Invariant 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.en-USBiologyImmunologyImmune CellsT CellsImmunityImmune DeficiencyImmunity to InfectionsInnate ImmunityMedicineInfectious DiseasesBacterial DiseasesMycobacteriumTuberculosisJournal Article2014-03-1110.1371/journal.ppat.1003805