|Kogut, Michael - Mike|
Submitted to: Journal of Interferon and Cytokine Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/7/2003
Publication Date: 6/20/2003
Citation: KOGUT, M.H., ROTHWELL, L., KAISER, P. DIFFERENTIAL REGULATION OF CYTOKINE GENE EXPRESSION BY AVIAN HETEROPHILS DURING RECEPTOR-MEDIATED PHAGOCYTOSIS OF OPSONIZED AND NON-OPSONIZED SALMONELLA ENTERITIDIS. JOURNAL OF INTERFERON AND CYTOKINE RESEARCH. 2003. v. 23. p. 319-327. 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 the 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: Internalization of pathogens by phagocytic cells triggers the innate immune response, which in turn regulates the acquired response. Phagocytes express a variety of receptors that are involved in recognition of pathogens including: (1) pathogen recognition receptors (PRRs) that recognize conserved motifs, (2) complement receptors (CR) that recognize complement-opsonized pathogens, and (3) Fc receptors (FcR) that recognize antibody-opsonized pathogens. Recognition of microbes is accompanied by the induction of multiple cell processes including the production of pro- and anti-inflammatory cytokines and chemokines. The objective of the present experiments was to use probes to known avian pro- and anti-inflammatory cytokines and TaqMan technology to ascertain levels of cytokine gene expression in avian heterophils following receptor-mediated phagocytosis of either nonopsonized Salmonella enteritidis (SE), serum opsonized SE, or IgG-opsonized SE. Expression of IL-6 and IL-8, considered in mammals as a pro-inflammatory chemokine, were up-regulated following exposure to the nonopsonized or the opsonized SE. However, mRNA expression for IL-18 and IFN-gamma were down-regulated while the expression of mRNA for the anti-inflammatory cytokine TGF-beta4 was up-regulated. Interestingly, IL-1beta mRNA expression was significantly up-regulated in heterophils that phagocytized either the nonopsonized SE via PRRs or IgG-opsonized SE via FcRs; whereas serum-opsonized SE phagocytized by CRs induced a down-regulation of IL-1beta mRNA. These results suggest that signaling interactions initiated by receptor recognition of the microbe surface, differentially regulate the induction of inflammatory cytokines in avian heterophils.