PT  - JOURNAL ARTICLE
AU  - Shuai Wang
AU  - Qianhong Ye
AU  - Ke Wang
AU  - Xiangfang Zeng
AU  - Shuo Huang
AU  - Haitao Yu
AU  - Qing Ge
AU  - Desheng Qi
AU  - Shiyan Qiao
TI  - Enhancement of Macrophage Function by the Antimicrobial Peptide Sublancin Protects Mice from Methicillin-Resistant <em>Staphylococcus aureus</em>
AID  - 10.1101/299305
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 299305
4099  - http://biorxiv.org/content/early/2018/04/11/299305.short
4100  - http://biorxiv.org/content/early/2018/04/11/299305.full
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is the major pathogen responsible for community and hospital bacterial infections. Sublancin, a glocosylated antimicrobial peptide isolated from Bacillus subtilis 168, possesses anti-bacterial infective effects. In this study, we investigated the role and anti-infection mechanism of sublancin in a mouse model of MRSA-induced sublethal infection. Sublancin could modulate innate immunity by inducing the production of IL-1β, IL-6, TNF-α and nitric oxide, enhancing phagocytosis and MRSA-killing activity in both RAW264.7 cells and peritoneal macrophages. The enhanced macrophage function by the peptide in vitro correlated with stronger protective activity in vivo in the MRSA-invasive sublethal infection model. Macrophages activation by sublancin was found to be mediated through the TLR4 and the NF-κB and MAPK signaling pathways. Moreover, oral administration of sublancin increased the frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes. The protective activity of sublancin was associated with in vivo augmenting phagocytotic activity of peritoneal macrophages and partly improving T cell-mediated immunity. Macrophages thus represent a potentially pivotal and novel target for future development of innate defense regulator therapeutics againt S. aureus infection.