iNKT Cell Production of GM-CSF Controls Mycobacterium tuberculosis

59Citations
Citations of this article
97Readers
Mendeley users who have this article in their library.

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 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. © 2014 Rothchild et al.

Cite

CITATION STYLE

APA

Rothchild, A. C., Jayaraman, P., Nunes-Alves, C., & Behar, S. M. (2014). iNKT Cell Production of GM-CSF Controls Mycobacterium tuberculosis. PLoS Pathogens, 10(1). https://doi.org/10.1371/journal.ppat.1003805

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free