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Title: Neutrophil function of neonatal foals is enhanced in vitro by CpG oligodeoxynucleotide stimulation

item BORDINA, ANGELA - Texas A&M University
item LIUA, MEI - Texas A&M University
item NERREN, JESSICA - Texas A&M University
item BUNTAIN, STEPHANIE - Texas A&M University
item BRAKE, COURTNEY - Texas A&M University
item Kogut, Michael - Mike
item COHEN, NOAH - Texas A&M University

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/17/2011
Publication Date: 1/15/2012
Citation: Bordina, A.I., Liua, M., Nerren, J.R., Buntain, S.L., Brake, C.N., Kogut, M.H., Cohen, N.D. 2012. Neutrophil function of neonatal foals is enhanced in vitro by CpG oligodeoxynucleotide stimulation. Veterinary Immunology and Immunopathology. 145:290-297.

Interpretive Summary: During the first few weeks after birth, the immune system of baby ponies is not very good at fighting bacterial infections such as Rhodococcus. We do not know the reason for this problem. The objective of this experiment was to look at a specific white blood cell (neutrophil) of the horse and determine whether the cells’ internal machinery could be controlled by providing a material found in bacterial DNA, but not horse DNA. We hoped that giving ponies this bacterial DNA will increase the ability of the pony’s immune system to respond to infections. We found that giving ponies this DNA that is found in all bacteria increased the ability of the pony’s immune system to respond to a Rhodococcus infection. In this way, the pony is able to use its own internal defenses to fight off a bacterial infection. The results of this experiment are important to the horse pharmaceutical industry in the United States because it shows that we can give a natural compound found in bacteria to stimulate the pony’s immune system to protect itself from infection. In addition, there is no danger of the bacteria developing resistance to the compound. This would result in a decrease in pony mortality.

Technical Abstract: Rhodococcus equi is an intracellular bacterium that causes pneumonia in foals and immunocompromised adult horses. Evidence exists that foals become infected with R. equi early in life, a period when innate immune responses are critically important for protection against infection. Neutrophils are innate immune cells that play a key role in defense against this bacterium. Enhancing neutrophil function during early life could thus help to protect foals against R. equi infection. The objective of our study was to determine whether in vitro incubation with the TLR9 agonist CpG 2142 would enhance degranulation and gene expression of cytokines and Toll-like receptor 9 (TLR9) by neutrophils collected from foals at 2, 14, and 56 days of life, and to determine whether these stimulated responses varied among ages. Neutrophil degranulation was enhanced at all ages by in vitro stimulation with either CpG alone, R. equi alone, or in combination with either R. equi or N-formyl-methionyl-leucyl-phenylalanine (fMLP) (P < 0.05), but not by in vitro stimulation with fMLP alone. There were no significant differences among ages in CpG-induced cytokine expression, except for IL-12p40, which was induced more at 56 days of age than on days 2 or 14. Collapsing data across ages, CpG 2142 significantly (P < 0.05) increased IL-6 and IL-17 mRNA expression. We concluded that in vitro stimulation of foal neutrophils with CpG enhances their function by promoting degranulation and inducing mRNA expression of IL-6 and IL-17, regardless of age.