Location: Food and Feed Safety Research
Title: Modulation of chicken intestinal gene expression by small cationic peptides as feed additives during the first week post-hatch Authors
Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 12, 2013
Publication Date: N/A
Interpretive Summary: There is a great deal of controversy concerning the use of antibiotics in animal feed. The biggest problem that critics have with this practice is the growing number of antibiotic-resistant bacteria that are causing disease in humans. These bacteria appear to come from meat products; therefore, we are interested in identifying chemicals that can protect animals from bacterial contamination without causing the bacteria to be resistant to antibiotics and other drugs that are used to treat human diseases. In this study, we added a newly discovered compound to chicken ration and fed it to baby chickens to see if it could protect the chicks from Salmonella infection. What makes this compound unique is that it has no direct killing effect on bacteria. We found that feeding this compound to the chicks did protect them from bacterial infection by “turning on” the chicks immune system. In this way, the chick was able to use its own internal defenses to fight off a bacterial infection. The results of this experiment are important to the pharmaceutical industry in the United States because they show that we can feed a compound to stimulate the chick’s immune system to protect itself from infection. In addition, there is no danger of the bacteria developing resistance to the compound because it has no direct effect on the bacteria. Thus, the number of antibiotic-resistant bacteria could drop dramatically in poultry meat products.
Technical Abstract: We have been investigating modulation strategies tailored around the selective stimulation of the host’s immune system as an alternative to direct targeting of microbial pathogens by antibiotics. One such approach is the use of a group of small cationic peptides (BT) produced by a Gram-positive soil bacterium, Brevibacillus texasporus. These peptides have immune modulatory properties that enhance both leukocyte functional efficiency and leukocyte pro-inflammatory cytokine and chemokine mRNA transcription activities in vitro. In addition, when provided as a feed additive for just 4 days post-hatch, BT peptides significantly induce a concentration-dependent protection against cecal and extra-intestinal colonization by Salmonella enterica serovar Enteritidis (SE). In the present studies, we assessed the effects of feeding BT peptides on transcriptional changes on pro-inflammatory cytokines, inflammatory chemokines, and Toll-like receptors (TLR) in the ceca of broiler chickens with and without SE infection. After feeding a BT peptide-supplemented diet for the first 4 days post-hatch, chickens were then challenged with SE and mucosal gene expression measured at 1 or 7 days post-infection (p.i.) (5 or 11 days of age). Intestinal expression of innate immune mRNA transcripts was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Analysis of relative mRNA expression showed that BT peptide-supplemented diets did not directly induce the transcription of pro-inflammatory cytokine, inflammatory chemokine, type I/II IFN, nor TLR mRNA in chicken cecum. However, feeding the BT peptide-supplemented diet primed cecal tissue for increased (P< 0.05) transcription of TLR4, 15, and 21 upon infection with SE on days 1 and 7 p.i. Likewise, feeding the BT peptides primed the cecal tissue for increased transcription of pro-inflammatory cytokines (IL-1ß, IL-6, IL-18, type I and II IFNs) and inflammatory chemokines (CxCLi1, CxCLi2) in response to SE infection 1 and 7 days p.i. when compared to the chickens fed the basal diet. These small cationic peptides may prove useful as alternatives to antibiotics as local immune modulators in neonatal poultry by providing prophylactic protection against Salmonella infections.