Induction of a macrophage-suppressive lymphokine by soluble cryptococcal antigens and its association with models of immunologic tolerance

Blackstock, Rebecca; McCormack, Jeffrey M.; Hall, Nancy K.

doi:10.1128/iai.55.1.233-239.1987

Cited by 35 publications

(17 citation statements)

References 25 publications

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“…54 In addition, injection of cryptococcal polysaccharide in mice resulted in immunosuppression with generation of T suppressor cells and release of an unidentified lymphokine that inhibited the microbicide function of macrophages. [27][28][29][30] It has also been demonstrated in mice that GXM in vivo inhibits leucocyte migration into sites of acute inflammation. 55 The results presented here demonstrate that the presence of GXM in the white pulp of spleen from normal rats impairs non-specific and specific lymphoproliferation with modification of normal cytokine synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…These reports have revealed immunological paralysis or suppression of the B lymphocyte response in mice inoculated with high doses of capsular polysaccharides or GXM. 25,26 In addition, Murphy and coworkers [27][28][29] have described a cascade of antigen-specific suppressor T cells that inhibited delayed-type hypersensitivity, and Blackstock et al 30 have observed a macrophage-suppressive lymphokine released by T cells after the injection of solubilized cryptococcal antigens in mice.…”

Section: Introductionmentioning

confidence: 99%

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Immunosuppression, interleukin‐10 synthesis and apoptosis are induced in rats inoculated with Cryptococcus neoformans glucuronoxylomannan

et al. 2004

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SUMMARYGlucuronoxylomannan (GXM) is the major Cryptococcus neoformans capsular polysaccharide and represents the main virulence factor of this fungus. In in vitro studies we have demonstrated previously that this acidic and high-molecular-weight polysaccharide suppresses lymphoproliferation, modulates cytokine production and promotes apoptosis in spleen mononuclear (Spm) cells from rats. In this study we demonstrate that these phenomena also occur in vivo after the intracardiac inoculation of GXM into normal Wistar rats. The results of this study show suppression of the proliferative response Spm cells to concanavalin A (Con A) or heat-killed C. neoformans (HKCn) in the first 2 weeks after polysaccharide administration. In addition, increased levels of interleukin (IL)-10 were produced by Con A-stimulated Spm cells, coinciding with immunohistochemical GXM detection in the white pulp of spleen. In particular, high production of IL-10 with diminution of IL-2, interferon (IFN)-c and tumour necrosis factor (TNF)-a synthesis were detected 14 days after GXM administration. In situ cell death detection by TdT-mediated biotin-dUTP nick-end labelling (TUNEL) reaction in sections of spleen, lung and liver demonstrates apoptosis in tissues with deposits of GXM. These data demonstrate the in vivo ability of GXM to modify cytokine synthesis by Spm cells and to promote host cell apoptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunosuppression, interleukin‐10 synthesis and apoptosis are induced in rats inoculated with Cryptococcus neoformans glucuronoxylomannan

et al. 2004

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“…The capsular polysaccharide of C. neoformans is associated with virulence and possesses a number of pathobiological properties, including specific inhibition of phagocytosis (8,22,35) and suppression of both antibody production and cell-mediated immune responses (2,3,19,29,30).…”

Section: Discussionmentioning

confidence: 99%

Killing of Cryptococcus neoformans strains by human neutrophils and monocytes

1991

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The susceptibility of various strains of Cryptococcus neoformans to killing by human polymorphonuclear leukocytes (PMNs) and monocytes was investigated. Five previously characterized strains of C. neoformans serotype A, a capsule-free mutant, and six recent clinical isolates were compared. PMNs and monocytes were isolated from normal peripheral blood and allowed to adhere to the flat-bottom wells of microtiter plates. Yeast cells of C. neoformans were added in the presence of normal human serum, and the plates were incubated at 37 degrees C. After 4 h, killing was determined by comparing the quantitative plate counts of viable yeast cells in experimental wells with counts in control wells containing yeast cells in the absence of leukocytes. No appreciable growth of yeast cells occurred in the wells during the incubation period. Both PMNs and monocytes effectively killed yeast cells at effector-to-target ratios as low as 1:1, although monocytes failed to kill the capsule-free strain 602 at a 1:1 ratio. With 9 of 12 strains, PMNs killed C. neoformans more effectively than did monocytes. Significant interstrain variation in killing occurred for both monocytes and PMNs, and the recent, clinical isolates were more resistant to killing by monocytes and PMNs than were the previously characterized strains. The extent to which different strains were killed by monocytes and PMNs was not consistently related to the size of the capsule or the entire cell. Normal PMNs and monocytes are remarkably effective in killing strains of C. neoformans in the absence of specific antibody and appear to constitute a significant defense mechanism in the peripheral circulation.

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“…Encapsulated C. neoformans strains have been shown to be weak stimulators of the macrophage respiratory burst compared with acapsular strains (172,175). Other immunosuppressive effects that have been attributed to the presence of capsule or purified CPS include down-regulation of cytokine secretion, inhibition of leukocyte accumulation, induction of suppressor T cells and suppressor factors, inhibition of antigen presentation, and inhibition of lymphoproliferation (15,25,51,78,179,182,208,211,295,296).…”

Section: Cryptococcus Neoformansmentioning

confidence: 99%

Virulence factors of medically important fungi

1996

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Human fungal pathogens have become an increasingly important medical problem with the explosion in the number of immunocompromised patients as a result of cancer, steroid therapy, chemotherapy, and AIDS. Additionally, the globalization of travel and expansion of humankind into previously undisturbed habitats have led to the reemergence of old fungi and new exposure to previously undescribed fungi. Until recently, relatively little was known about virulence factors for the medically important fungi. With the advent of molecular genetics, rapid progress has now been made in understanding the basis of pathogenicity for organisms such as Aspergillus species and Cryptococcus neoformans. The twin technologies of genetic transformation and "knockout" deletion construction allowed for genetic tests of virulence factors in these organisms. Such knowledge will prove invaluable for the rational design of antifungal therapies. Putative virulence factors and attributes are reviewed for Aspergillus species, C. neoformans, the dimorphic fungal pathogens, and others, with a focus upon a molecular genetic approach. Candida species are excluded from coverage, having been the subject of numerous recent reviews. This growing body of knowledge about fungal pathogens and their virulence factors will significantly aid efforts to treat the serious diseases they cause.

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Induction of a macrophage-suppressive lymphokine by soluble cryptococcal antigens and its association with models of immunologic tolerance

Cited by 35 publications

References 25 publications

Immunosuppression, interleukin‐10 synthesis and apoptosis are induced in rats inoculated with Cryptococcus neoformans glucuronoxylomannan

Immunosuppression, interleukin‐10 synthesis and apoptosis are induced in rats inoculated with Cryptococcus neoformans glucuronoxylomannan

Killing of Cryptococcus neoformans strains by human neutrophils and monocytes

Virulence factors of medically important fungi

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