|Kogut, Michael - Mike|
Submitted to: Molecular Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/15/2003
Publication Date: 12/1/2003
Citation: Kogut, M.H., Rothwell, L., Kaiser, P. 2003. Priming by recombinant chicken interleukin-2 induces selective expression of IL-8 and IL-18 MRNA in chicken heterophils during receptor-mediated phagocytosis of opsonized and nonopsonized Salmonella enterica serovar enteritidis. Molecular Immunology. 40:603-610. Interpretive Summary: During the first week of life after hatching and for reasons still unclear, the immune system of the baby chick is not very good at fighting against bacterial infections such as Salmonella. However, there are chemicals in the body of baby chicks called cytokines that 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 chemicals or not. We found that heterophils do produce some of these cytokines when they come in contact with Salmonella. However, some cytokines 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 cytokines 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 cytokines which will help the chick fight Salmonella infections.
Technical Abstract: Recognition of microbes by phagocytic cells is accompanied by the induction of multiple cell 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. Heterophils, the principal avian PMN equivalent to the mammalian neutrophil, function as professional phagocytes against bacterial infections, mediate acute inflammation, and respond to cytokine stimulation to aid in regulation of innate host defenses. Priming of phagocytes is the potentiation of the activation process by previous exposure to a priming agent. Interleukin-2 (IL-2) has been found to exercise an array of biological effects on other cell types besides T lymphocytes, including NK cells, B cells, monocytes, and neutrophils. In the present experiments, using real-time quantitative RT-PCR, we evaluated the role of rChIL-2 as a priming mediator controlling heterophil responses at the level of gene transcription by examining the expression of mRNA for pro-inflammatory (IL-1beta, IL-6, IL-8) and Th1 (IL-18 and IFN-gamma) cytokine genes following stimulation with phagocytosis agonists; i.e., opsonized and nonopsonized Salmonella enteritidis. Peripheral blood heterophils were isolated and incubated with various concentrations of rChIL-2 from transfected COS cells. rChIL-2 selectively primed the heterophils for an increase in transcription of the pro-inflammatory cytokine IL-8 and of theTh1 cytokine IL-18 induced by all three phagocytic agonists. Although rChIL-2 priming modulated the expression of specific cytokine mRNA in heterophils stimulated by different phagocytic agonists, the rChIL-2 by itself did not directly induce gene expression of either the pro-inflammatory or Th1 cytokines. We propose that rChIL-2 could be priming heterophils solely to function as more efficient innate effector cells to limit bacterial growth through the selective increase of IL-8 and IL-18 gene expression.