Mechanisms of Invariant NKT Cell Activity in Restraining Bacillus anthracis Systemic Dissemination

Exogenous activation of invariant NKT (iNKT) cells by the superagonist α-galactosylceramide (α-GalCer) can protect against cancer, autoimmune diseases, and infections. In the current study, we investigated the effect of α-GalCer against Bacillus anthracis infection, the agent of anthrax. Using an experimental model of s.c. B. anthracis infection (an encapsulated nontoxigenic strain), we show that concomitant administration of α-GalCer delayed B. anthracis systemic dissemination and prolonged mouse survival. Depletion of subcapsular sinus CD169-positive macrophages by clodronate-containing liposome was associated with a lack of iNKT cell activation in the draining lymph nodes (dLNs) and prevented the protective effect of α-GalCer on bacterial dissemination out of the dLNs. Production of IFN-γ triggered chemokine (C-C motif) ligand 3 synthesis and recruitment of neutrophils in the dLNs, leading to the restraint of B. anthracis dissemination. Our data highlight a novel immunological pathway leading to the control of B. anthracis infection, a finding that might lead to improved therapeutics based on iNKT cells.

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