The most important findings of our study are: i) CXCR2 is a critical driver of tissue neutrophilia after CDI; ii) IL-1β is a key molecular mediator in the gut-bone marrow axis that promotes CXCR2 upregulation and CDI-induced colonic neutrophil accrual; and iii) IL-1β concentration is differentially regulated based on host SNP type. Here, CXCR2 is linked to clostridium difficile infection.