Macrophage selenoproteins restrict intracellular replication of Francisella tularensis

• Published in: The Journal of immunology (1950) 2017-05, Vol.198 (1_Supplement), p.148-148.12
• Main Authors: Markley, R L., Williamson, David R., Katkere, Bhuvana, Dewan, Kalyan K., Shay, Ashley E., Sumner, Sarah E., Prabhu, K. Sandeep, Kirimanjeswara, Girish S
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.198.Supp.148.12

There has been a growing appreciation for the influence of dietary nutrients on the microbiome as well as host response to infectious disease. The micronutrient selenium (Se) is known to regulate immune functions via selenoproteins, a class of proteins that contain the 21st amino acid selenocysteine. However, the mechanisms by which selenoproteins regulate immune functions during an acute infection are not clear. Therefore, we investigated the role of macrophage (Mac) selenoproteins during an acute bacterial infection. Francisella tularensis (Ft.), the causative agent of tularemia, is a gram-negative intracellular bacterium. Since Ft. infects and replicates primarily in Macs, we measured the bacterial replication in Macs derived from TrspM mice that are unable to synthesize selenoproteins. TrspM Macs had uncontrolled replication of Ft. compared to wild-type (WT) Macs. Moreover, TrspM mice were more susceptible to Ft. infection and harbored significantly higher levels of bacteria in their livers and spleens as compared to WT mice, which suggests that Mac selenoproteins are essential for restricting bacterial replication and promoting host survival. Since Ft. replication is closely associated with autophagy, we investigated if the Mac selenoproteins had an effect on autophagy. In fact, our data indicates that selenoproteins inhibit autophagy, which may limit the availability of nutrients to the bacteria. Future studies will seek to establish the influence of selenoproteins on the microbiome and how these changes impact the infectious disease process. Our studies demonstrate that nutrients affect the outcome of an infection by influencing host immune response, and reveal potential novel targets for antibacterial therapies.