A SYSTEMS BIOLOGY APPROACH TO UNDERSTANDING THE SALMONELLA-HOST INTERACTOME IN POULTRY AND SWINE
Location: Food and Feed Safety Research
Title: BT cationic peptides: Small peptides that modulate innate immune responses of chicken heterophils and monocytes
Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 31, 2011
Publication Date: November 6, 2011
Citation: Kogut, M.H., Genovese, K.J., He, L.H., Swaggerty, C.L., Jiang, Y. 2011. BT cationic peptides: Small peptides that modulate innate immune responses of chicken heterophils and monocytes. Veterinary Immunology and Immunopathology. 145:151-158.
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 chick's 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.
Drug-resistant bacteria pose an enormous threat to public health having developed resistance mechanisms to all existing classes of antibiotics. Fewer novel antibiotics are being developed, so there is an increasing need to identify alternative approaches with less associated resistance. An alternative approach to antibiotics involves facilitating pathogen-specific host immune responses. BT peptides are a group of cationic peptides produced by a Gram-positive soil bacterium, Brevibacillus texasporus. We have previously shown that, provided as a feed additive, BT peptides significantly induced a concentration-dependent protection against cecal colonization and extraintestinal colonization by Salmonella enterica serovar Enteritidis (SE). This protection is not the result of direct antibacterial activity of the BT peptides on the SE since the concentrations used were below the minimum inhibitory concentration for SE. We also found that BT are not absorbed in the intestine but still induce a significant up-regulation in the functional efficiency of peripheral blood heterophils and monocytes. The mechanisms of this immune modulation are unknown. Here, using in vitro models for measuring: (1) leukocyte oxidative burst, (2) changes in leukocyte cytokine and chemokines gene expression profiles, and (3) phosphorylation of the mitogen activated protein kinases (MAPK) in leukocytes, we evaluated the role of BT peptides as priming mediators for heterophil and monocyte responses at the level of cell function, gene transcription/expression, and cell phosphorylation following stimulation with inflammatory agonists. BT peptides primed both heterophils and monocytes for an increased oxidative burst and up-regulation in transcription of the pro-inflammatory cytokines IL-1ß and IL-6 and inflammatory chemokines CxCLi1 and CxCLi2 induced by inflammatory agonists. In addition, BT peptides induced a rapid (10 min) phosphorylation and activation of the extracellular signal-regulated kinase (ERK 1/2) and p38 kinase pathways in primary chicken heterophils. Taken together, we conclude that BT peptides, acting through MAPK pathways, enhance leukocyte functional and pro-inflammatory cytokine and chemokine gene transcription activities. These small cationic peptides may prove useful as alternatives to antibiotics as anti-infective therapeutics in poultry.