| First Author | Rothchild AC | Year | 2014 |
| Journal | PLoS Pathog | Volume | 10 |
| Issue | 1 | Pages | e1003805 |
| PubMed ID | 24391492 | Mgi Jnum | J:248319 |
| Mgi Id | MGI:5918871 | Doi | 10.1371/journal.ppat.1003805 |
| Citation | Rothchild AC, et al. (2014) iNKT cell production of GM-CSF controls Mycobacterium tuberculosis. PLoS Pathog 10(1):e1003805 |
| abstractText | 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. |
