Differential Regulation of Cytokine Gene Expression by Avian Heterophils During Receptor-Mediated Phagocytosis of Opsonized and Nonopsonized Salmonella enteritidis

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) pattern recognition receptors (PRR), which recognize conserved motifs, (2) complement receptors (CR), which recognize complement-opsonized pathogens, and (3) Fc receptors (FcR), which recognize antibody-opsonized pathogens. Recognition of microbes is accompanied by the induction of multiple cell processes, including the production of proinflammatory and anti-inflammatory cytokines and chemokines. The objective of the present experiments was to use probes to known avian proinflammatory 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 interleukin-6 (IL-6) and IL-8, considered in mammals as a proinflammatory chemokine, were upregulated following exposure to the nonopsonized or the opsonized SE. However, mRNA expression for IL-18 and interferon-γ (IFN-γ) was downregulated, and the expression of mRNA for the anti-inflammatory cytokine transforming growth factor-β4 (TGF-β 4) was upregulated. Interestingly, IL-1β mRNA expression was significantly upregulated 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 downregulation of IL-1β 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.