| First Author | Kyme P | Year | 2012 |
| Journal | J Clin Invest | Volume | 122 |
| Issue | 9 | Pages | 3316-29 |
| PubMed ID | 22922257 | Mgi Jnum | J:190743 |
| Mgi Id | MGI:5449645 | Doi | 10.1172/JCI62070 |
| Citation | Kyme P, et al. (2012) C/EBPepsilon mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice. J Clin Invest 122(9):3316-29 |
| abstractText | The myeloid-specific transcription factor, CCAAT/enhancer-binding protein epsilon (C/EBPepsilon) is a critical mediator of myelopoiesis. Mutation of this gene is responsible for neutrophil-specific granule deficiency in humans, a condition that confers susceptibility to Staphylococcus aureus infection. We found that C/EBPepsilon-deficient mice are severely affected by infection with S. aureus, and C/EBPepsilon deficiency in neutrophils contributes to the infectious phenotype. Conversely, exposure to the epigenetic modulator nicotinamide (vitamin B3) increased expression of C/EBPepsilon in WT myeloid cells. Further, nicotinamide increased the activity of C/EBPepsilon and select downstream antimicrobial targets, particularly in neutrophils. In a systemic murine infection model as well as in murine and human peripheral blood, nicotinamide enhanced killing of S. aureus by up to 1,000 fold but had no effect when administered to either C/EBPepsilon-deficient mice or mice depleted of neutrophils. Nicotinamide was efficacious in both prophylactic and therapeutic settings. Our findings suggest that C/EBPepsilon is an important target to boost killing of bacteria by the innate immune system. |
