Functional SLC11A1 (NRAMP1) enhances protection from <i>Coxiella burnetii</i> infection

Abstract SLC11A1 is a divalent ion transporter formerly known as the natural resistance-associated macrophage protein (NRAMP1). Also known as the Bcg/Lsh/Ity locus, SLC11A1 was originally characterized as the resistance factor for Mycobacterium, Leshmania, and Salmonella infections. This protein is non-functional in C57BL/6 mice, thus, the susceptibility of this strain to these pathogens. We recently characterized the expression of SLC11A1 in the majority of γδ T cells and NK cells, which are primary sources of innate IFN-γ. Cells expressing SLC11A1 were more prone to activation. We hypothesized that SLC11A1 would have an important function in infections in which IFN-γ was a critical component. Only two genes have been described as potential susceptibility loci for Q fever caused by Coxiella burnetii infection, they are IFN-γ and SLC11A1 in humans. Thus, we assessed C. burnetii infection in congenic mice with and without functional SLC11A1. SLC11A1+ mice had improved disease symptoms, harbored fewer bacteria, and had increased expression of innate cytokines, including IFN-γ. The results indicate that mice expressing functional SLC11A1 were more resistant to infection with C. burnetii, suggesting an expanded role for this protein in innate immune protection.

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