|Kogut, Michael - Mike|
Submitted to: Journal of Interferon and Cytokine Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/2/2004
Publication Date: 2/1/2005
Citation: Kogut, M.H., Rothwell, L., Kaiser, P. 2005. IFN-y priming of chicken heterophils upregulates the expression of proinflammatory and TH1 cytokine mRNA following receptor-mediated phagocytosis of Salmonella enterica serovar enteritidis. Journal of Interferon and Cytokine Research. 25:73-81. Interpretive Summary: During the first week of life after hatching, the immune system of the baby chick is not very good at fighting bacterial infections such as Salmonella. We do not know the reason for this problem. However, there are chemicals in the body of baby chicks called cytokines. These chemicals control the way baby chicks fight infections. The objective of this experiment was to look at a specific white blood cell of the chicken - called the heterophil-and determine whether the cells' internal machinery can produce these chemical reactions or not. We found that heterophils do produce some of these chemicals when they come in contact with Salmonella. However, some of these chemicals are not produced which can cause a problem in baby chicks when infected with Salmonella. The results of this experiment are important to the pharmaceutical industry in the United States because we now know which chemicals are produced (or not) by the baby chick's cells of the immune system when they see Salmonella. Thus, we can now see if there are ways for us to get the baby chick to make these chemicals which will help the chick fight Salmonella infections.
Technical Abstract: The immediate response to invasive pathogens, clearance via the inflammatory response, and activation of the appropriate acquired responses are all coordinated and orchestrated by the innate host defenses. Recognition of microbes is accompanied by the induction of multiple cellular processes including the production of pro- and anti-inflammatory cytokines. Polymorphonuclear leukocytes (PMNs) are vital cellular components of innate immunity, and function by killing pathogenic microbes following phagocytosis. The primary PMN in poultry is the heterophil. Priming is the potentiation of the phagocyte activation process by previous exposure to a priming agent. IFN-gamma is a pleiotrophic cytokine involved in basically all phases of immune and inflammatory responses that has been shown to prime heterophil functional activities. In the present experiments, using real-time quantitative RT-PCR, we evaluated the role of rChIFN-gamma as a priming mediator to control heterophil responses at the level of gene transcription and expression of the mRNA for proinflammatory (IL-1beta, IL-6, IL-8) and Th1 (IL-18 and IFN-gamma) cytokine genes following stimulation with phagocytosis agonists opsonized and nonopsonized Salmonella enteritidis. rChIFN-gamma primed the heterophils for an increase in transcription of pro-inflammatory cytokines induced by phagocytic agonists, but also upregulated expression of Th1 cytokine (IL-18 and IFN-gamma) mRNA. Although rChIFN-gamma priming modulated the expression of cytokine mRNA in heterophils stimulated by different phagocytic agonists, rChIFN-gamma by itself did not directly induce gene expression of either proinflammatory or Th1 cytokines. The enhanced expression of cytokine mRNA does not appear to be differentially expressed depending on the receptor activated during phagocytosis. The results from the present experiments suggest that rChIFN-gamma may play a significant role in avian innate immunity against Salmonella infection and may offer an adjunct use in the prevention and treatment of salmonellae infections in newly hatched chickens