One of the leading causes of hospital-acquired infection in immune compromised patients is the fungus, Candida albicans. Among patients, both the risk of developing candidiasis and the clinical outcome is variable, indicating that host-dependent factors contribute to C. albicans infection and disease progression. Using a murine candidiasis model, Michail Lionakis and colleagues at the National Institute of Allergy and Infectious Diseases determined that C. albicans interacts with macrophages in the kidney during the initial stages of infection and this interaction is mediated by the chemokine receptor CX3CR1. Mice lacking this receptor succumbed to C. albicans-induced kidney failure; however, these mice had exhibited fungal clearance in other organs prior to death. Furthermore, human patients with a mutation in the gene encoding CX3CR1 were at higher risk of candidiasis. This study identifies an important role for CX3CR1-meditated interaction of C. albicans and macrophages in controlling disease progression and outcome. The micrographs above are representative sections from PAS-stained murine kidney. In the kidney of WT mice (left), C. albicans (magenta) is contained within distinct foci: however, in the kidney of Cx3cr1-/- mice (right), C. albicans is seen throughout the tissue.
Michail S. Lionakis, Muthulekha Swamydas, Brett G. Fischer, Theo S. Plantinga, Melissa D. Johnson, Martin Jaeger, Nathaniel M. Green, Andrius Masedunskas, Roberto Weigert, Constantinos Mikelis, Wuzhou Wan, Chyi-Chia Richard Lee, Jean K. Lim, Aymeric Rivollier, John C. Yang, Greg M. Laird, Robert T. Wheeler, Barbara D. Alexander, John R. Perfect, Ji-Liang Gao, Bart-Jan Kullberg, Mihai G. Netea, Philip M. Murphy