Meeting Abstract
Staphylococcus aureus is a common cause of hospital-acquired illness worldwide, with ~14 million US patients seeking treatment for infections each year. While the outcomes of S. aureus exposure can range from asymptomatic colonization to fatal infection, the factors influencing the severity of infection are not fully understood. Host genetics can play a significant role in disease susceptibility, and identifying genes relevant to susceptibility to specific pathogens, including S. aureus, may be important for predicting which populations are more vulnerable to life-threatening infection. Previous work in our lab identified three chromosomes (8, 11, and 18) associated with susceptibility to S. aureus infection in A/J mice, along with several candidate genes with human orthologues that may be particularly important. Our current work focuses on the Crif1 gene, located on chromosome 8. Downregulation of Crif1 is associated with apoptosis, a key player in the control of immune response. We used the primary murine macrophage model to compare phagocytosis, replication, and cytokine production in bone marrow-derived macrophages (BMDM) isolated from Crif1 knockout mice and C57BL/6 (B6), an established wild type control for S. aureus resistance. Preliminary results show no difference in phagocytosis of S. aureus by BMDM as determined by colony forming units. The intracellular S. aureus replication in BMDM was comparable in both mouse lines. Finally, using the Luminex-bead based assay, we found that the cytokines IL-6, IL-12, MCP-1, and MIP-1α were higher in Crif1 BMDM compared to B6. Our preliminary data suggests that Crif1 plays an important role in host immune response, and may lead to increased susceptibility to S. aureus infection when absent.
