Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cryptococcus”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed1977

Non-encapsulated variant of Cryptococcus neoformans. II. Surface receptors for cryptococcal polysaccharide and their role in inhibition of phagocytosis by polysaccharide.

The binding of cryptococcal polysaccharide to a non-encapsulated strain of Cryptococcus neoformans was studied. Binding of purified polysaccharide to the yeast was determined by inhibition of phagocytosis and by indirect immunofluorescence techniques. The ability of cryptococcal polysaccharide to prevent phagocytosis of the non-encapsulated strain appears to be directly related to adherence of polysaccharide to the yeast via specific receptors on the cell surface. Addition of varying doses of cryptococcal polysaccharide to non-encapsulated yeast cells inhibited phagocytosis only at polysaccharide concentrations at which the polysaccharide could be demonstrated on the yeast surface by immunofluorescence. Macrophages treated with cryptococcal polysaccharide had no detectable amounts of cryptococcal polysaccharide adherent to their surface, and they had a normal ability to phagocytize the yeast. Kinetic studies showed that inhibition of phagocytosis is directly related to the presence of cryptococcal polysaccharide at the yeast surface rather than to some indirect effect by the polysaccharide on serum components necessary for phagocytosis. Purified polysaccharide from C. neoformans serotypes A, B, C, and D bound to the yeast, but type III pneumococcal polysaccharide did not inhibit phagocytosis of the nonencapsulated yeast. Cryptococcal polysaccharide did not bind to cells of Candida albicans, C. pseudotropicalis, Torulopsis sp., Rhodotorula sp., or Saccharomyces cerevisiae.

Ascitic Fluid↗
PubMed1977

Cryptococcus neoformans: size range of infectious particles from aerosolized soil.

Although cryptococcosis is characterized as a chronic central nervous system disease, it is generally accepted that the lungs are the primary portal of entry for the etiological agent. Despite this, there is a distinct lack of evidence that viable airborne particles of Cryptococcus neoformans are small enough to reach the alveoli. Two encapsulated strains and one nonencapsulated strain of C. neoformans were inoculated into 250-g quantities of sterile soil. Throughout the 0 to 12 weeks of incubation, this soil was aerosolized in a sealed chamber with a Waring blender. Samples of the resultant dust cloud were taken with an Anderson air sampler from which the numbers and sizes of viable airborne particles were determined. Of the viable organisms aspirated into the air sampler, 15% were 0.65 to 2 micron in diameter. As incubation time in soil increased, the size of the particles decreased, and increased numbers of C. neoformans cells 0.65 to 2 micron in diameter were isolated. The presence of viable cells less than 2 micron in soil aerosols indicated that, under certain conditions in nature, C. neoformans cells exist in sizes that are capable of deep lung deposition.

Aerosols↗
PubMed1977

Immune response to Cryptococcus neoformans soluble polysaccharide: immunological unresponsiveness.

Mice injected with 100 to 800 microgram of Cryptococcus neoformans soluble polysaccharide showed a reduced ability to produce antibody after a challenge immunization with polysaccharide emulsified in Freund incomplete adjuvant. These animals were considered immunologically unresponsive. Animals given an initial injection of 25 or 50 microgram of polysaccharide responded to a challenge immunization in the same manner as control animals. Reversion of unresponsive mice to antibody production without further antigenic stimulation did not occur during a 12-week experimental period. These animals exhibited a partial response to challenge immunization 8 weeks after induction of unresponsiveness, and they were fully responsive to challenge immunization at 12 weeks. Animals given a single dose of 0.1, 0.4, or 1.6 microgram of polysaccharide produced a marked anamnestic response after challenge immunization. Repeated injections of subimmunogenic doses of polysaccharide did not produce a marked anamnestic response and would induce unresponsiveness only when the cumulative dose reached 100 to 400 microgram of polysaccharide, suggesting that injected cryptococcal polysaccharide might be sequestered in some manner until an amount of antigen sufficient for induction of unresponsiveness is accumulated. This possibility was confirmed by immunofluorescence studies that revealed a long-term deposition of polysaccharide in the tubular epithelial cells of the kidney.

Animals↗
PubMed1978

Cryptococcus neoformans: pseudohyphal forms surviving culture with Acanthamoeba polyphaga.

During experiments on the gastrointestinal tract as a possible portal of entry for Cryptococcus neoformans, we occasionally observed the free-living amoeba, Acanthamoeba polyphaga, growing in the presence of C. neoformans cultured from mouse feces. Examination of the amoebic trophozoites revealed that they were engorged with yeast cells. Over a period of 2 to 3 weeks of incubation, the amoebae apparently killed most of the yeast cells. Some of the surviving C. neoformans cells formed atypical colonies which contained pseudohyphae. Seven other strains have since been cultured with this amoeba. Pseudohyphal forms were found among the surviving colonies in all strains tested. Virulence studies were performed on one randomly selected pseudohyphal isolate from each of the eight strains of C. neoformans. Pseudohyphal isolates from seven of the eight strains failed to kill mice 30 days after intracranial inoculation. The potential role of soil amoebae in the control of C. neoformans in nature is discussed.

Amoeba↗
PubMed1978

Phagocytosis of Cryptococcus neoformans by normal and thioglycolate-activated macrophages.

Phagocytosis of Cryptococcus neoformans by normal and thioglycolate-activated mouse peritoneal macrophages was studied. Thioglycolate-activated macrophages exhibited a lower percent phagocytosis than did normal macrophages. Differences in phagocytosis could not be attributed to differences in macrophage viability, minor variations in the concentration of adherent macrophages, or a general depression in activated macrophage phagocytosis. Thioglycolate-activated macrophages required heat-labile opsonins for optimal phagocytosis of non-encapsulated cryptococci, whereas nonactivated macrophages did not require heat-labile opsonins for phagocytosis of the yeast. Both types of macrophages exhibited similar sensitivity to the phagocytosis-inhibiting properties of cryptococcal polysaccharide. The results show that depletion of heat-labile opsonins from serum or inactivation of yeast-bound, heat-labile opsonins by polysaccharide cannot account for the phagocytosis-inhibiting properties of cryptococcal polysaccharide.

Animals↗
PubMed1978

Delayed-type hypersensitivity responses in infected mice elicited by cytoplasmic fractions of Cryptococcus neoformans.

Four subcellular fractions of Cryptococcus neoformans prepared by differential centrifugation of disrupted whole yeast and a 3-day culture filtrate were examined for their ability to elicit delayed-type hypersensitivity in sensitized animals. The methods used to detect sensitization were (i) the footpad swelling test and inhibition of peritoneal macrophage migration in mice and (ii) skin testing in guinea pigs. Two entities, the post-mitochondrial supernatant and the culture filtrate, showed considerable activity in the footpad test, with 26- and 30-microliter 24-h swellings, respectively, at 6 weeks after infection. With the latter there was interference from a strong antibody-mediated 4-h skin reaction. The post-mitochondrial supernatant produced strong delayed-type hypersensitivity in guinea pigs at a dose of 69 microgram, and there was no demonstrable cross-reactivity in animals sensitized with heterologous fungi. The footpad swelling in mice correlated well with the macrophage migration inhibition test, with 71% inhibition in mice infected subcutaneously with C. neoformans at 6 weeks. However, mice infected intravenously developed poorer cell-mediated immunity than the subcutaneously infected mice. The post-mitochondrial supernatant was found to contain detectable amounts of cryptococcal capsular polysaccharide.

Animals↗
PubMed1979

Kinetics of lymphocyte transformation in mice immunized with viable avirulent forms of Cryptococcus neoformans.

A murine model was developed to study the cell-mediated immune response of mice immunized with one of two live, avirulent forms of Cryptococcus neoformans: a nonencapsulated mutant and a thinly encapsulated pseudohyphal variant. A lymphocyte transformation assay was used to evaluate the cellular response of control and sensitized spleen cells after in vitro incubation with three merthiolate-killed whole-cell antigens of C. neoformans. An antigen-to-spleen cell ratio of 10:1 and 5 days of incubation of antigen-spleen cell mixtures were established as optimal conditions for maximum lymphocyte transformation. Maximum responses occurred from 2 to 3 weeks after the last of eight weekly intraperitoneal inoculations of C. neoformans. This assay provided an accurate, reproducible method of studying cell-mediated immunity to C. neoformans, and applications to the study of cryptococcal pathogenesis are proposed.

Animals↗
PubMed1979

Opsonization of Cryptococcus neoformans by human immunoglobulin G: role of immunoglobulin G in phagocytosis by macrophages.

The role of immunoglobulin G (IgG) as an opsonin in phagocytosis of Cryptococcus neoformans by macrophages was investigated. Labeling with 125I showed that IgG isolated from normal human serum bound to non-encapsulated C. neoformans. Furthermore, IgG-opsonized cryptococci were agglutinated by anti-serum to IgG heavy chains, indicating that normal human serum contains antibody that will bind to the yeast surface. The IgG isolated from normal serum accounted for all opsonizing activity found in normal human serum, since differences were not noted between the opsonizing activities of whole serum, heat-inactivated serum and purified IgG when these opsonins were compared at equivalent concentrations of IgG. Phagocytosis of IgG-opsonized cryptococci was inhibited by anti-macrophage IgG, a reagent known to block Fc-mediated attachment and ingestion, and by pepsin digestion of opsonizing IgG. Thus, IgG opsonization is an Fc-dependent process. Opsonizing IgG appears to play its major role during the attachment phase of phagocytosis, since antimacrophage IgG blocked attachment of cryptococci to macrophages but could not block ingestion of IgG-opsonized cryptococci that had been allowed to attach to macrophages. Ingestion of opsonized cryptococci was not blocked by 2-deoxy-D-glucose, a reagent known to block Fc-mediated ingestion, thus confirming that IgG has a primary role in attachment and suggesting that ingestion is mediated by a process that is not Fc dependent.

Agglutination↗
PubMed1979

Opsonization of Cryptococcus neoformans by human immunoglobulin G: masking of immunoglobulin G by cryptococcal polysaccharide.

Previous studies have shown that attachment of non-encapsulated cryptococci to macrophages is highly dependent on opsonizing immunoglobulin G (IgG) and that cryptococcal polysaccharide inhibits the attachment phase of phagocytosis. We investigated various mechanisms by which cryptococcal polysaccharide might interfere with the opsonizing action of IgG. Cryptococcal polysaccharide did not appreciably prevent binding of opsonizing IgG to the yeast. Furthermore, cryptococcal polysaccharide acted as a noncompetitive inhibitor with respect to the opsonizing action of IgG. These experiments suggested that cell wall-bound IgG is masked in some manner such that it is unable to participate in Fc-mediated phagocytosis. This appeared to be the case, since cryptococcal polysaccharode inhibited agglutination of IgG-opsonized yeast cells by antiserum to IgG. There was good dose-response correlation between the amount of polysaccharide needed to inhibit phagocytosis of non-encapsulated Cryptococcus neoformans and the amount of polysaccharide needed to prevent agglutination of IgG-opsonized cryptococci by antiserum to IgG. The ability of cryptococcal polysaccharide to prevent agglutination of IgG-opsonized cryptococci by antiserum to IgG was lost if dextran, a substance known to enhance agglutination of several particles, was incorporated into the medium.

Agglutination↗
PubMed1979

Chemotaxigenesis and activation of the alternative complement pathway by encapsulated and non-encapsulated Cryptococcus neoformans.

In the presence of serum, whole cells of encapsulated and non-encapsulated Cryptococcus neoformans generated a chemotactic response by neutrophils. Heat inactivation of serum ablated all chemotactic activity. Cryptococcal polysaccharide was not chemotaxigenic. Assays for alternative complement pathway activation such as depletion of alternative complement pathway factor B or electrophoretic conversion of factor B closely paralleled chemotaxis assays. Cells of encapsulated and non-encapsulated C. neoformans activated the alternative complement pathway, whereas cryptococcal polysaccharide was inactive. Failure of the capsular material to activate the alternative pathway was not due to serotype specificity because polysaccharide of several serotypes failed to achieve activation. The results suggest that chemotaxigenesis and alternative complement pathway activation are functions of the yeast cell wall. The results support our proposal that the cryptococcal capsul does not prevent potential opsonins from reaching binding and activation sites at the yeast cell wall or the release of biologically active soluble cleavage products into the surrounding medium; however, cell wall-bound cleavage products remain bound to the cell wall beneath the capsule. Therefore, they are unable to participate as opsonins in phagocytosis.

Animals↗
PubMed1980

Isolation and characterization of arginine auxotrophs of Cryptococcus neoformans.

Arginine auxotrophs were isolated in both mating types of Cryptococcus neoformans. In both mutants, the auxotrophy was due to the lack of active argininosuccinate lyase. The virulence in mice of the mutants was compared with that of the wild type. One auxotroph displayed a loss of virulence which appeared to be related to the presence of another mutation, one which prevented normal cell separation after budding. The other auxotroph had reduced virulence compared with the wild type, but a variant isolated from it by mouse passage had virulence equivalent to that of the wild type while maintaining the auxotrophic requirements.

Animals↗
PubMed1980

Transfer of immunity to cryptococcosis by T-enriched splenic lymphocytes from Cryptococcus neoformans-sensitized mice.

Splenic enriched T-cells and sera were obtained from inbred CBA/J mice injected 7 or 35 days earlier with either 10(3) viable Cryptococcus neoformans or sterile physiological saline. The transfer of enriched T-cells collected 7 days after immunization or of normal enriched T-cells did not transfer immunity to C. neoformans or delayed-type hypersensitivity responsiveness to cryptococcal culture filtrate (CneF) antigen to the recipients. However, enriched T-cells harvested 35 days after immunization, when transferred to recipient mice, were able to confer immunity as indicated by the reduction in numbers of C. neoformans cells in the tissues, and they also transferred delayed-type hypersensitivity responsiveness to CneF antigens. Sera from either sensitized or normal mice were unable to transfer immunity to recipient animals. These results suggested that there was a time requirement for development of the immune response in the donor mice and that T-cells were crucial in the host defense against a cryptococcal infection. Culturing of day-35 C. neoformans-sensitized T-cells in the presence of homologous antigen (CneF) but not in the presence of heterologous antigen (purified protein derivative or 2, 4-dinitro-1-fluorobenzene) induced the production of migration inhibition factor, thus indicating that lymphocytes from C. neoformans-injected mice were specifically sensitized to CneF antigen.

Animals↗
PubMed1981

Distribution of Cryptococcus neoformans in a natural site.

Pigeon droppings in a vacant tower were assayed for the number and size of viable cells of Cryptococcus neoformans. The dry, thinly scattered floor debris contained 2.6 x 10(6) viable cells per g--300 times more cells than were cultured from a large, compact pile of pigeon droppings (7.4 x 10(3) cells per g). Aerosols generated from floor debris containing pigeon droppings had an average of 360 viable cells in 31 liters of air; 27 of these cells (7.5%) were 1.1 to 3.3 micrometers in diameter and, therefore, capable of human lung deposition. Environmental factors which may influence the distribution, survival, and proliferation of C. neoformans in nature are discussed.

Aerosols↗
PubMed1981

Immediate hypersensitivity to Cryptococcus neoformans.

The role of the capsular polysaccharide in anaphylactic reactions to Cryptococcus neoformans was investigated. Groups of mice were sensitized with viable cells of either a moderately encapsulated strain of C. neoformans or a non-encapsulated variant. Anaphylactic reactions were observed in both groups of mice to a similar extent when challenged with whole cells. Mice sensitized with the encapsulated strain and challenged with homologous polysaccharide showed only mild hypersensitivity symptoms. Mice sensitized with either the encapsulated or the nonencapsulated strain showed cross-reactivity when challenged with killed cells of the heterologous strain. These data indicate that the capsular polysaccharide plays a minor role in anaphylactic reactions to C. neoformans and that the sensitizing antigen is probably located in the cell wall of the yeast.

Anaphylaxis↗
PubMed1981

Opsonization of encapsulated Cryptococcus neoformans by specific anticapsular antibody.

Antisera prepared in rabbits against either whole encapsulated cells of Cryptococcus neoformans or purified cryptococcal polysaccharide were opsonic for the encapsulated yeast. The opsonic activity was removed by absorption with whole cryptococci and was inhibited by free polysaccharide. As little as 0.13 microgram of cryptococcal polysaccharide produced a 50% inhibition of opsonization. Various degrees of neutralization by polysaccharides from the four cryptococcal serotypes suggested that the opsonins were type specific. Fractionation of antiserum on Bio-Gel A-5m (Bio-Rad Laboratories) and diethylaminoethyl cellulose showed that the opsonins were antibodies of the immunoglobulin G class. These opsonizing antibodies did not require heat-labile serum components for optimal phagocytosis of the yeast. Inhibition studies using 2-deoxy-D-glucose demonstrated that ingestion of encapsulated cryptococci opsonized with anticapsular antibody was a 2-deoxy-D-glucose-inhibitable process. This result differed from similar studies with non-encapsulated cryptococci which showed that ingestion of non-encapsulated cryptococci opsonized with normal serum was not inhibited by 2-deoxy-D-glucose.

Animals↗
PubMed1982

Immunization of mice by intracutaneous inoculation with viable virulent Cryptococcus neoformans: immunological and histopathological parameters.

Immune responses, including protection and delayed hypersensitivity, were evaluated in experimental murine cryptococcosis. Mice were immunized by the intracutaneous inoculation of viable virulent Cryptococcus neoformans yeasts. Response to the cutaneous infection was evaluated histologically and by cultural assays of the internal organs, as well as by intravenous challenge with the same strain. Protection was assessed by survival, histopathology, and quantitative organ culture. The intracutaneous inoculation of cryptococci resulted in a local inflammatory response that effectively limited dissemination of the organisms systemically and induced the development of delayed hypersensitivity demonstrable with a membrane extract of C. neoformans and with soluble cytoplasmic substances. A protective response was induced by the cutaneous inoculation of cryptococci as well, in that immunized animals survived longer, with about 25% of the challenged group ridding themselves completely of the cryptococci. Protection could be demonstrated by cultural analyses, but all animals, whether control or immunized, allowed considerable multiplication of the inoculum during the first 4 weeks after intravenous challenge. It would appear, therefore, that the protective mechanism(s) required additional antigenic stimulation before it could eventually function to eliminate all cryptococci from tissues. Histologically, there were no differences in pathology of the internal organs between immunized and unimmunized animals. Although the model described herein for the induction of immune responses in murine cryptococcosis has at least one drawback, viz., the presence of cryptococci in the skin lesion of many animals throughout the duration of the experiment, it does have the advantage that the immune responses were stimulated by a virulent strain and only minimal dissemination occurred. Therefore, lymphocytes could be removed from animals that were not contaminated with cryptococci for in vitro and in vivo transfer.

Animals↗
PubMed1982

In vitro interactions of immune lymphocytes and Cryptococcus neoformans.

CBA/J mice immunized subcutaneously with emulsions of heat-killed Cryptococcus neoformans in complete Freund adjuvant displayed delayed-type hypersensitivity to cryptococcal culture filtrate antigen and developed sensitized splenic lymphoid cells which inhibited the growth of C. neoformans in vitro. The in vitro assay of growth inhibition served to investigate further the kinetics of the effect of sensitized lymphoid cells on the pathogen. There was a close correlation between the delayed-type hypersensitivity response in mice and inhibition of growth of C. neoformans by lymphoid cells. Sensitized splenic lymphocytes capable of inhibiting the growth of the cryptococci were detected at day 6 after immunization and reached maximum levels by days 8 through 16. Inhibition of growth was highest with effector-to-target cell ratios of 300:1 or greater. Inhibition of growth of C. neoformans by sensitized lymphoid cells was detectable as early as 4 h after effector and target cells were mixed and increased gradually, reaching a maximum at 24 h, but dropped significantly by 48 h. By supplementing the reaction mixtures with fresh medium or additional sensitized effector cells during incubation, the inhibition of growth of C. neoformans could be maintained through 48 h. C. neoformans-sensitized effector lymphoid populations not only inhibited the growth of the pathogen in vitro but also restricted C. neoformans proliferation in various vital organs upon transfer to naive recipient animals, indicating that the in vitro growth inhibition assay may be a means of assessing the resistance of animals to C. neoformans. The effector cells from sensitized animals were nylon wool-nonadherent Thy-1+ and Ia+ lymphocytes.

Animals↗
PubMed1982

Phenoloxidase activity and virulence in isogenic strains of Cryptococcus neoformans.

A naturally occurring Mel- variant of Cryptococcus neoformans was isolated from the wild type. The effect of phenoloxidase activity on virulence was analyzed on genetically constructed Mel+ and Mel- isolates. The traits Mel+ and virulence in mice, as measured by cumulative mortality and replication potential in brain tissue, cosegregated among the progeny of a Mel+ X Mel- cross. Revertants (MelR) isolated during the course of the cumulative mortality experiment were used to compare virulence in isogenic sets of Mel- and MelR. In two separate sets of such isolates, Mel+ phenotype and virulence coreverted. Measurement of substrate uptake and phenoloxidase activity showed that loss of detectable phenoloxidase was the basis for the Mel- phenotype and that enzyme activity reappeared in the MelR isolates. An intermediate phenotype, Melbg, was also described. Cosegregation and coreversion of the melanin phenotype and virulence suggest that phenoloxidase is a virulence factor in C. neoformans.

Catechol Oxidase↗