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.
Highlights
Cathelicidins are host defense peptides (HDPs) with antimicrobial activity and immunomodulatory functions
avian pathogenic E. coli (APEC) induced CATH‐B1 gene expression in macrophages CATH-B1 protein has so far only been detected in the bursa of Fabricius, but CATH-B1 mRNA is found in different tissues including the respiratory tract, gastrointestinal tract and lymphoid organs [23], indicating that a broader expression of CATH-B1 is likely
The effect of CATH‐B1 on phagocytosis in macrophages To determine the effect of CATH-B1 on the function of macrophages, the peptide was added to primary macrophages or HD11 cells together with APEC
Summary
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]. CATH-2 has broad antimicrobial activity and strong immunomodulatory effects, such as lipopolysaccharide (LPS) binding, neutralization of the immune response and enhanced DNA-induced activation of toll like receptor (TLR) 21 [9,10,11,12]. Less is known about the activities of CATH-B1, which means that it is challenging to properly compare functionalities and activities [14]. One clear difference between CATH-1, -2, -3 and CATH-B1 is apparent: using immunostaining and mass
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