Group B streptococci (GBS) are a major cause of severe infection in newborns, pregnant females, and other immunocompromised hosts. Infection often includes septicemia, shock, pneumonia, and respiratory failure. In previous studies, we have reported that GBS induce marked production of tumor necrosis factor alpha (TNF-␣) by human mononuclear cells. The present study was designed to measure the production of TNF-␣ as well as additional cytokines, including interleukin 1 (IL-1), IL-6, IL-8, IL-12, and gamma interferon (IFN-␥) but also to determine from what cells and at what time point during incubation with GBS that these cytokines are produced. Mixed mononuclear cells were incubated with heat-killed GBS, media alone, or 1 g of Escherichia coli lipopolysaccharide (LPS). Brefeldin A was added to each sample prior to staining, which prevented the export of cytokines by the Golgi apparatus. The cells were then stained with the appropriate conjugated antibodies and analyzed by using a flow cytometer. Results indicate that intracellular cytokines appear, in almost all cases, simultaneous to or before secreted proteins are detected. In contrast to the response to LPS, where TNF-␣, IL-1, IL-6, and IL-8 appear almost simultaneously, the human monocyte response to GBS results in the production of TNF-␣ but delayed appearance of IL-1, IL-6, and IL-8. The lymphocyte response to GBS was also strikingly different from that to LPS in that both secreted IFN-␥ and IL-12 was detected, while LPS failed to induce production of these critical cytokines. This suggests an important role for TNF-␣, IFN-␥, and IL-12 in GBS pathogenesis and/or immunity.
Invertebrate hosts of chemoautotrophic symbionts face the unique challenge of supplying their symbionts with hydrogen sulfide while avoiding its toxic effects. The sulfur-containing free amino acids taurine and thiotaurine may function in sulfide detoxification by serving as sulfur storage compounds or as transport compounds between symbiont and host. After sulfide exposure, both taurine and thiotaurine levels increased in the gill tissues of the symbiotic coastal bivalve Solemya velum. Inhibition of prokaryotic metabolism with chloramphenicol, inhibition of eukaryotic metabolism with cycloheximide, and inhibition of ammonia assimilation with methionine sulfoximine reduced levels of sulfur-containing amino acids. Chloramphenicol treatment inhibited the removal of sulfide from the medium. In the absence of metabolic inhibitors, estimated rates of sulfide incorporation into taurine and thiotaurine accounted for nearly half of the sulfide removed from the medium. In contrast, amino acid levels in the nonsymbiotic, sulfide-tolerant molluscs Geukensia demissa and Yoldia limatula did not change after sulfide exposure. These findings suggest that sulfur-containing amino acids function in sulfide detoxification in symbiotic invertebrates, and that this process depends upon ammonia assimilation and symbiont metabolic capabilities.
Human neonates are uniquely susceptible to group B streptococcal (GBS) infections. We have shown that neonatal mixed mononuclear cells have a deficiency in the production of the T helper-1 (Th-1) cytokine, interferon gamma (IFN-␥), and that incubation of neonatal neutrophils with recombinant IFN-␥ corrects these neutrophil defects. IL-12 and the more recently described IL-18 are also Th-1 type cytokines that are able to induce the production of IFN-␥ in the presence of bacteria and bacterial products. We examine the ability of GBS to induce the production of IFN-␥, IL-18, and IL-12 by cord blood mixed mononuclear cells and compared these results with the IFN-␥, IL-18, and IL-12 response of mixed mononuclear cells from adult blood. We demonstrate that cord blood mixed mononuclear cells produced significantly less IL-18 is a recently described member of the IL-1 cytokine family, which was initially defined as IFN-␥-inducing factor (1). IL-18 gene expression and/or protein secretion has been observed in macrophages (2), dendritic cells (3), mononuclear cells (4), keratinocytes (5), chondrocytes (6), pituitary and adrenal cells (7), astrocytes and microglia (8), and intestinal epithelial cells (9). Studies have elucidated a broad array of effector functions implicating IL-18 as an important regulator of both innate and acquired immune responses (10, 11). In animals, IL-18 contributes to protective immunity against a variety of pathogens, including Cryptococcus, Leishmania, Staphylococcus, Salmonella,.IL-12 is also an integral immune regulator, which promotes Th-1 responses while suppressing Th-2 responses (16,17). IL-12 is primarily produced by macrophages and dendritic cells and has been shown to induce the production of IFN-␥ by T cells and natural killer (NK) cells (18). Recent studies have focused on the interaction between IL-18 and IL-12 in certain inflammatory responses. In Th-1 immune responses, IL-18 and IL-12 are important cytokines that may synergistically stimulate IFN-␥ production and enhance NK and T cell-mediated cytotoxicity (19). Recent studies implicate the interaction of these Th-1 cytokines in the development of autoimmune diseases and suggest that regulating their function may be therapeutically beneficial (20,21).Early-onset GBS infections in neonates often lead to sepsis and severe septic shock, with an approximate 5-15% mortality rate (22)(23)(24)
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