Salmon nasal cartilage proteoglycan up-regulates Listeria monocytogenes-mediated immune response in mice

Proteoglycan (PG) is a complex glycohydrate that is widely distributed in the extracellular matrix. We have reported that daily oral administration of PG extracted from salmon (<i>Oncorhynchus keta</i>) nasal cartilage modulates the severity and proinflammatory cytokine responses in <i>Escherichia coli-</i>stimulated macrophages, and attenuates mouse models of various inflammatory diseases. Thus, PG has shown anti-inflammatory activities. In this study, we investigated the effect of salmon nasal cartilage PG on a bacterial infection by using a mouse model of infection with <i>Listeria monocytogenes</i>, which is a facultative intracellular pathogen. PG enhanced production of cytokines including TNF-α, IL-6, IL-12 and IL-10 by heat-killed <i>L. monocytogenes</i> in macrophages and dendritic cells. Daily oral administration of PG inhibited proliferation of <i>L. monocytogenes</i> in the livers of infected mice. IFN-γ and IL-12 production was enhanced in the PG-treated mice. Uptake of <i>L. monocytogenes</i> cells by PG-treated macrophages was decreased, followed reduction of intracellular bacteria growth. Differential proteomic analysis of mouse liver revealed that positive and negative immunological molecules for host defense against <i>L. monocytogenes</i> infection were modulated by PG treatment. These results demonstrated that PG can activate immune responses for host defense against <i>L. monocytogenes</i> infection through augmentation of cytokines and limiting infection of macrophages. The present study indicates that PG possesses quite different potentials, depending on the host conditions.