Effect of Leptin Receptor Q223R Polymorphism on Clostridioides difficile Infection-Induced Macrophage Migration Inhibitory Factor Production

Proinflammatory cytokine levels and host genetic makeup are key determinants of Clostridioides difficile infection (CDI) outcomes. We previously reported that blocking the inflammatory cytokine macrophage migration inhibitory factor (MIF) ameliorates CDI. Here, we determined kinetics of MIF production and its association with a common genetic variant in leptin receptor (LEPR) using blood from patients with CDI. We found highest plasma MIF early after C difficile exposure and in individuals who express mutant/derived LEPR. Our data suggest that early-phase CDI provides a possible window of opportunity in which MIF targeting, potentially in combination with LEPR genotype, could have therapeutic utility. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine elevated in the plasma of patients with Clostridioides difficile infection (CDI). We explored the kinetics of MIF and the effect of leptin receptor single-nucleotide polymorphism on systemic MIF levels of CDI patients. Graphical Abstract