Publications by authors named "Daniel S Korbel"

Cryptosporidiosis is an important diarrheal disease of humans and neonatal livestock caused by Cryptosporidium spp. that infect epithelial cells. Recovery from Cryptosporidium parvum infection in adult hosts involves CD4(+) T cells with a strong Th1 component, but mechanisms of immunity in neonates are not well characterized.

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Rapid cell-mediated immune responses, characterized by production of proinflammatory cytokines, such as IFN-gamma, can inhibit intraerythrocytic replication of malaria parasites and thereby prevent onset of clinical malaria. In this study, we have characterized the kinetics and cellular sources of the very early IFN-gamma response to Plasmodium falciparum-infected RBCs among human PBMCs. We find that NK cells dominate the early (12-18 h) IFN-gamma response, that NK cells and T cells contribute equally to the response at 24 h, and that T cells increasingly dominate the response from 48 h onward.

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Type II interferon (IFN), IFN-gamma, is important in innate immunity to the intestinal protozoan parasite Cryptosporidium species, which infects epithelial cells (enterocytes). This investigation is, to our knowledge, the first to characterize the role of type I IFN in innate immunity to this parasite. Pretreatment of human or murine enterocyte cell lines with IFN-alpha/beta inhibited parasite development, and we identified that a key mechanism of cytokine action was to prevent parasite invasion of enterocytes.

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A gamma interferon (IFN-gamma)-dependent innate immune response operates against the intestinal parasite Cryptosporidium parvum in T- and B-cell-deficient SCID mice. Although NK cells are a major source of IFN-gamma in innate immunity, their protective role against C. parvum has been unclear.

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The apicomplexan parasite Cryptosporidium parvum, the agent of cryptosporidiosis, primarily infects and reproduces in enterocytes. Interferon (IFN)-gamma is important for early control of the infection and acts directly on enterocytes to inhibit parasite development, although complete inhibition is not obtained. Addressing this latter observation, an investigation was made of the modulatory effect of C.

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IFN-gamma emanating from NK cells is an important component of innate defense against infection. In this study, we demonstrate that, following in vitro stimulation of human peripheral blood NK cells with a variety of microbial ligands, CD56(dim) as well as CD56(bright) NK cells contribute to the overall NK cell IFN-gamma response with, for most cell donors, IFN-gamma(+) CD56(dim) NK cells outnumbering IFN-gamma(+) CD56(bright) NK cells. We also observe that the magnitude of the human NK IFN-gamma response to microbial ligands varies between individuals; that the antimicrobial response of CD56(bright), but not CD56(dim), NK cells is highly correlated with that of myeloid accessory cells; and that the ratio of IFN-gamma(+) CD56(dim) to IFN-gamma(+) CD56(bright) NK cells following microbial stimulation differs between individuals but remains constant for a given donor over time.

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Tuberculosis is the most important bacterial infection world wide. The causative agent, Mycobacterium tuberculosis survives and proliferates within macrophages. Immune mediators such as interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) activate macrophages and promote bacterial killing.

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Data from a variety of experimental models suggest that natural killer (NK) cells require signals from accessory cells in order to respond optimally to pathogens, but the precise identity of the cells able to provide such signals depends upon the nature of the infectious organism. Here we show that the ability of human NK cells to produce interferon-gamma in response to stimulation by Plasmodium falciparum-infected red blood cells (iRBCs) is strictly dependent upon multiple, contact-dependent and cytokine-mediated signals derived from both monocytes and myeloid dendritic cells (mDCs). Contrary to some previous reports, we find that both monocytes and mDCs express an activated phenotype following short-term incubation with iRBCs and secrete pro-inflammatory cytokines.

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Human NK cells can respond rapidly to Plasmodium falciparum-infected RBC (iRBC) to produce IFN-gamma. In this study, we have examined the heterogeneity of this response among malaria-naive blood donors. Cells from all donors become partially activated (up-regulating CD69, perforin, and granzyme) upon exposure to iRBC but cells from only a subset of donors become fully activated (additionally up-regulating CD25, IFN-gamma, and surface expression of lysosomal-associated membrane protein 1 (LAMP-1)).

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Natural killer (NK) cells are lymphoid cells that mediate significant cytotoxic activity and produce high levels of pro-inflammatory cytokines in response to infection. During viral infection, NK cell cytotoxicity and cytokine production is induced principally by monocyte-macrophage- and dendritic cell-derived cytokines but virally encoded ligands for NK cells are also beginning to be described. NK derived interferon-gamma (IFN-gamma) production is also essential for control of several protozoal infections including toxoplasmosis, trypanosomiasis, leishmaniasis and malaria.

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