Abstract
Antibiotic resistance has been considered to be a global threat which underscores the need to develop novel anti-infective therapeutics. Modulation of innate immunity by synthetic peptides is an attractive strategy to overcome this circumstance. We recently reported that BCCY-1, a human β-casein-derived peptide displays regulatory activities on monocytes, thereby enhancing their actions in innate immune responses. However, the function of peptide BCCY-1 in host defense against infection remains unknown. In this study, we investigated the in vivo characteristics and effects of peptide BCCY-1 in mouse models of bacterial infection. Following intraperitoneal injection, the peptide BCCY-1 exhibited high level of cellular uptake by monocytes without obvious toxicities. Results revealed that peptide BCCY-1, but not the scrambled version, stimulated the chemokine production and monocyte recruitment in vivo. Treatment with BCCY-1 enhanced the pathogen clearance and protected mice against lethal infections. Because the anti-infective effects of BCCY-1 was abolished by in vivo depletion of monocytes/macrophages rather than lymphocytes and granulocytes, we conclude that monocytes/macrophages are key effector cells in BCCY-1-mediated anti-infective protection. Additionally, BCCY-1 lacks direct antimicrobial activity. To our knowledge, a human β-casein-derived peptide that counters infection by selective regulation of innate immunity has not been reported previously. These results suggest peptide BCCY-1 as a promising alternative approach and a valuable complement to current anti-infective strategy.
Highlights
The discovery of antibiotics is considered the greatest achievement in treatment of infections
These findings suggested that BCCY-1 showed good system circulation that might contribute to a higher uptake and the subsequent modulatory effects of BCCY-1 in monocytes
We found that depletion of monocytes/macrophages using clodronate liposomes abrogated the protective activity of BCCY-1 (Figures 5A, B), while protection was still observed in mice deficient in T/B lymphocytes (Figure 5C) and neutrophils (Figure 5D), confirming the pivotal role for monocytes/ macrophages in BCCY-1-mediated protection
Summary
The discovery of antibiotics is considered the greatest achievement in treatment of infections. Their excessive use has resulted in the emergence of drug-resistant bacteria [1]. Modulation of the innate immune response, the first line of defense against infections, thereby enhancing its capacity to elimination of pathogens is an attractive way as it is consistent with antibiotic therapies but may reduce or avoid concerns of drug-resistant bacteria and has broader applications. A Novel Anti-Infective Peptide BCCY-1 regulation and development of the neonatal immune function [2]. We recently reported that peptide BCCY-1 has great immunomodulatory effects on monocytes in vitro [9], illustrating its potential in anti-infective therapy which needs to be further investigated
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