Abstract: The present invention demonstrates the important role of C/EBP? in innate immune response against pathogens. Specifically, the inventors showed that in the absence of functional C/EBP?, mice are severely impaired in their ability to clear S. aureus infection. Neutrophils are particularly affected, and susceptibility to S. aureus can be rectified by treatment with interferon-gamma (IFN-?). Importantly, increased activity of C/EBP?, either by induced overexpression of C/EBPE or by application of nicotinamide or an analog, derivative or salt thereof, dramatically enhances immune killing of S. aureus and leads to amelioration of infection.

Abstract: Cationic antimicrobial peptides (AMPs) are an integral part of the innate immune system. Cathelicidin and defensin homologs from a variety of species exhibit broad-range bactericidal activity. The human cathelicidin analog, hCAP18, is encoded by the CAMP gene. Vitamin D3 and its analogs upregulate transcription of CAMP and defensin ?2 (defB2) genes, leading to increased expression of hCAP18 mRNA and defB2. Induction of CAMP was observed in acute myeloid leukemia (AML), immortalized keratinocyte and colon cancer cell lines, as well as normal human bone marrow (BM)-derived macrophages and fresh BM cells.