The homozygous CX3CR1-M280 mutation impairs human monocyte survival

• DOI: 10.1172/jci.insight.95417
• Publication Date: 2018-02-07T16:01:03Z
• Authors: Amanda L. Collar; Muthulekha Swamydas; Morgan O’Hayre; Md Sanaullah Sajib; Kevin W. Hoffman; Satya P. Singh; Ahmad Mourad; Melissa D. Johnson; Elise M.N. Ferre; Joshua M. Farber; Jean K. Lim; Constantinos M. M...; J. Silvio Gutkind; Michail S. Lionakis
• Keywords: CX3CR1; Monocyte; CX3CL1

Several reports have demonstrated that mouse Cx3cr1 signaling promotes monocyte/macrophage survival. In agreement, we previously found that, in a model of systemic candidiasis, genetic deficiency resulted increased mortality and impaired tissue fungal clearance associated with decreased macrophage We translated this finding by showing the dysfunctional CX3CR1 variant CX3CR1-M280 was risk worse outcome human candidiasis. However, impact mutation on survival is poorly understood. Herein, hypothesized impairs monocyte identified WT (CX3CR1-WT/WT), CX3CR1-WT/M280 heterozygous, CX3CR1-M280/M280 homozygous healthy donors European descent, show CX3CL1 rescues serum starvation–induced cell death CX3CR1-WT/WT but not monocytes. CX3CL1-induced monocytes mediated via AKT ERK activation, which are both monocytes, blood counts at steady state. Instead, does affect surface expression or innate immune effector functions. Together, homozygocity M280 polymorphism potentially novel population-based factor influences signaling.