Immunomodulation and effects on microbiota after in ovo administration of chicken cathelicidin-2

Abstract

Host Defense Peptides (HDPs) such as cathelicidins are multifunctional effectors of the innate immune system with both antimicrobial and pleiotropic immunomodulatory functions. Chicken cathelicidin-2 (CATH-2) has multiple immunomodulatory effects in vitro and the D-amino acid analog of this peptide has been shown to partially protect young chicks from a bacterial infection. However, the mechanisms responsible for CATH-2 mediated in vivo protection have not been investigated so far. In this study, D-CATH-2 was administered in ovo and the immune status and microbiota of the chicks were investigated at 7 days posthatch to elucidate the in vivo mechanisms of the peptide. In three consecutive studies, no effects on numbers and functions of immune cells were found and only small changes were seen in gene expression of Peripheral Blood Mononuclear Cells (PBMCs). In two studies, intestinal microbiota composition was determined which was highly variable, suggesting that it was strongly influenced by environmental factors. In both studies, in ovo D-CATH-2 treatment caused significant reduction of Ruminococcaceae and Butyricicoccus in the cecum and Escherichia/Shigella in both ileum and cecum. In conclusion, this study shows that, in the absence of an infectious stimulus, in ovo administration of a CATH-2 analog alters the microbiota composition but does not affect the chicks’ immune system posthatch.

Immunometabolism: new insights and lessons from antigen-directed cellular immune responses

“…Several studies have gone further to show that LL-37 has anti-cancer properties based on its ability to kill cancer cells in vitro (reviewed by Kuroda et al in [269]). LL-37 bioavailability in the colon, however, can affect gut microbiota viability and potentially perpetrate dysbiosis, as shown in chickens in the context of CATH-2 [270]. However, mice lacking the antimicrobial peptide CRAMP (CRAMP-KO) displayed oral dysbiosis following co-housing with wildtype mice, possibly transferred to the gut of the CRAMP-KO animals due to CRAMP presence in the feces of the latter [271].…”

Development of innate immunity in chicken embryos and newly hatched chicks: a disease control perspective

“…As constituents of the neutrophil extracellular traps (Brinkmann, 2004) and nanonets in the intestine (Chu et al, 2012), HDPs can trap bacteria before intestinal translocation. HDPs can influence gut microbiota composition by influencing the expression of PRRs by intestinal epithelial cells (Tang et al, 2016;Cuperus et al, 2018). In addition to their effects on innate immunity, HDPs can boost adaptive immunity through the regulation of chemotaxis, maturation and activation of lymphocytes and DCs (Davidson et al, 2004).…”

Associations between phenotypic characteristics and clinical parameters of broilers and intestinal microbial development throughout a production cycle: A field study

“…Therefore, knowledge of the development and variation of intestinal microbiota composition is pivotal for the design of strategies toward optimizing the intestinal health of broiler flocks. In poultry, it has been observed that the gut microbiota composition varies between flocks, flock cycles, breeds, and housing conditions and that many other unknown host and environmental factors exist (Cuperus, Kraaij, Zomer, van Dijk, & Haagsman, 2018; Johnson et al, 2018; Kers, Velkers, et al, 2019; Kers et al, 2018; Kim et al, 2015; Stanley, Geier, Hughes, Denman, & Moore, 2013).…”