Abstract
Mast cells (MCs) play a significant role in the innate immune defense against bacterial infection through the release of cytokines and antimicrobial peptides. However, their antimicrobial function is still only partially described. We therefore hypothesized that MCs express additional antimicrobial peptides. In this study, we used FANTOM 5 transcriptome data to identify for the first time that MCs express lipocalin 2 (LCN2), a known inhibitor of bacterial growth. Using MCs derived from mice which were deficient in LCN2, we showed that this antimicrobial peptide is an important component of the MCs’ antimicrobial activity against Escherichia coli (E. coli). Since sphingosine-1-phosphate receptors (S1PRs) on MCs are known to regulate their function during infections, we hypothesized that S1P could activate LCN2 production in MCs. Using an in vitro assay, we demonstrated that S1P enhances MCs antimicrobial peptide production and increases the capacity of MCs to directly kill S. aureus and E. coli via an LCN2 release. In conclusion, we showed that LCN2 is expressed by MCs and plays a role in their capacity to inhibit bacterial growth.
Highlights
Mast cells (MCs) are known to be key mediators of allergic inflammation in peripheral tissues
Based on a transcriptome analysis of human MCs, FANTOM 5 data [11], we found that lipocalin 2 (LCN2), a molecule that binds to bacterial siderophores inhibiting bacterial growth [12], is present in MCs
Transcriptome analysis showed that dermal Human MCs (hMCs) express LCN2, and interestingly, it is expressed at higher levels in the skin MCs compared to in culture-expanded MCs
Summary
Mast cells (MCs) are known to be key mediators of allergic inflammation in peripheral tissues. MCs, when activated in response to pathogens, secrete preformed cytokines that facilitate the development, amplification, and regulation of the innate immune response. Current literature supports the concept that MCs express different innate immune receptors, such as Toll-like receptors (TLRs), that initiate pathogen recognition [3,4]. MCs can be activated to directly kill pathogens by phagocytosis or through antimicrobial peptide (AMP) release [5,6]. We have previously published that during bacterial or viral encounters MCs secrete cathelicidin, an AMP, and directly kill bacteria and viruses [7,8]. CAMP is the only human, cathelicidin-derived AMP that is present in MCs [9]. While CAMP in MCs has been extensively studied, other antimicrobial proteins have not been investigated. We show for the first time that LCN2 is secreted by MCs and enhances their antimicrobial function
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