The immunomodulatory effect of cathelicidin-B1 on chicken macrophages
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RESEARCH ARTICLE
Open Access
The immunomodulatory effect of cathelicidin‑B1 on chicken macrophages Lianci Peng, Maaike R. Scheenstra, Roel M. van Harten, Henk P. Haagsman and Edwin J. A. Veldhuizen*
Abstract Cathelicidins (CATHs) play an important role in the innate immune response against microbial infections. Among the four chicken cathelicidins, CATH-B1 is studied the least. In this study, the effect of CATH-B1 on the macrophage response towards avian pathogenic E. coli (APEC) and bacterial ligands was investigated. Our results show that APEC induced CATH-B1 gene expression in both a chicken macrophage cell line (HD11 cells) and primary macrophages, while expression of the other three CATHs was virtually unaffected. While the antimicrobial activity of CATH-B1 is very low under cell culture conditions, it enhanced bacterial phagocytosis by macrophages. Interestingly, CATH-B1 downregulated APEC-induced gene expression of pro-inflammatory cytokines (IFN-β, IL-1β, IL-6 and IL-8) in primary macrophages. In addition, CATH-B1 pre-incubated macrophages showed a significantly higher gene expression of IL-10 after APEC challenge, indicating an overall anti-inflammatory profile for CATH-B1. Using isothermal titration calorimetry (ITC), CATH-B1 was shown to bind LPS. This suggests that CATH-B1 reduces toll like receptor (TLR) 4 dependent activation by APEC which may partly explain the decreased production of pro-inflammatory cytokines by macrophages. On the contrary, direct binding of CATH-B1 to ODN-2006 enhanced the TLR21 dependent activation of macrophages as measured by nitric oxide production. In conclusion, our results show for the first time that CATH-B1 has several immunomodulatory activities and thereby could be an important factor in the chicken immune response. Keywords: chicken, innate immunity, macrophages, antimicrobial peptides, cathelicidins, E. coli Introduction Cathelicidins are host defense peptides (HDPs) with antimicrobial activity and immunomodulatory functions. They are produced as inactive precursors (prepropeptides), stored in granules, and upon cell activation released as mature peptides by proteolytic cleavage [1]. Cathelicidins have been found in many different species, including mammals, reptiles, amphibians, fishes and birds [2, 3]. Interestingly, the number of functional genes encoding cathelicidins in different species is highly variable [4]. For example, only a single cathelicidin (LL-37) is present in human, while chicken has four cathelicidins *Correspondence: [email protected] Department of Biomolecular Health Sciences, Division of Infectious Diseases & Immunology, Section of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584CL Utrecht, The Netherlands
with varying length and structure (CATH-1, -2, -3 and -B1) [5–8]. Of the four chicken cathelicidins, CATH-2 has been studied extensively. CATH-2 has broad antimicrobial activity and strong immunomodulatory effects, such as lipopolysaccharide (LPS) binding, neutralization of the immune respo
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