Cell-mediated immunity in cryptococcosis

Graybill, John R.; Alford, Robert H.

doi:10.1016/0008-8749(74)90164-6

Cited by 114 publications

(57 citation statements)

References 20 publications

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“…Mice developed granulomatous inflammation, a finding consistent with prior literature, which is indicative of a cell-mediated immune response (28,47). However, in several murine pulmonary infection models, cellular immunity is insufficient to control infection in the lung, and mice die with large pulmonary fungal burdens (18,20,32).…”

Section: Discussionsupporting

confidence: 83%

Cryptococcus neoformansIs a Facultative Intracellular Pathogen in Murine Pulmonary Infection

Feldmesser

Kress²,

Novikoff³

et al. 2000

Infect Immun

408

413

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To produce chronic infection, microbial pathogens must escape host immune defenses. Infection with the human pathogenic fungus Cryptococcus neoformans is typically chronic. To understand the mechanism by which C. neoformans survives in tissue after the infection of immunocompetent hosts, we systematically studied the course of pulmonary infection in mice by electron microscopy. The macrophage was the primary phagocytic cell at all times of infection, but neutrophils also ingested yeast.

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Section: Discussionsupporting

confidence: 83%

Cryptococcus neoformansIs a Facultative Intracellular Pathogen in Murine Pulmonary Infection

Feldmesser

Kress²,

Novikoff³

et al. 2000

Infect Immun

408

413

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“…Thus, if one excludes abnormalities resulting either from concurrent disease, such as malignancy, or administration of exogenous drugs such as chemotherapeutic agents, transitory defects in both in vitro and in vivo cell-mediated immunity, abnormalities in in vitro proliferative responses but not in the elaboration of lymphokines, as well as normal proliferative responses accompanied by defects in either release or effect of lymphokines, have all been reported to occur in patients infected with various fungal organisms. Moreover, it is evident from the studies presented here and by others that there is a subpopulation of patients with fungal infection who demonstrate severe, persistent defects of their in vivo as well as in vitro T-cell reactivity (2,30,34). The crucial finding demonstrated by this study is that this defect may not result from a lack of potentially reactive T cells but rather may result from a suppression of this reactivity by other non-Ig-bearing, nonphagocytic, S-RBC rosette-forming, and thus presumably T cells.…”

Section: Methodsmentioning

confidence: 55%

“…Additionally, both T-and B-cell reactivity can be affected by an increasing list of soluble substances which may be produced exogenously by other nonlymphoid cells (24)(25)(26)(27)(28). This variety of mechanisms by which immunologic reactivity may be impaired is reflected by the heterogeneity of immunologic defects detected in patients with fungal infection; some of which are depicted by the three groups of patients indicated here and many of which have been reported previously (2,3,(29)(30)(31)(32)(33)(34). Thus, if one excludes abnormalities resulting either from concurrent disease, such as malignancy, or administration of exogenous drugs such as chemotherapeutic agents, transitory defects in both in vitro and in vivo cell-mediated immunity, abnormalities in in vitro proliferative responses but not in the elaboration of lymphokines, as well as normal proliferative responses accompanied by defects in either release or effect of lymphokines, have all been reported to occur in patients infected with various fungal organisms.…”

Section: Methodsmentioning

confidence: 66%

Suppressor thymus-derived lymphocytes in fungal infection.

Stobo¹,

Paul²,

Scoy³

et al. 1976

J. Clin. Invest.

235

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“…This clinical observation, in addition to animal studies, has made it clear that T-cell-mediated immunity is of paramount importance in host defense against C. neoformans (1,7,15,19,20,22,28,31). T-cell immunity is antigen specific; however, we have recently shown that T cells are also capable of responding to C. neoformans by an alternate mechanism of activation (36).…”

mentioning

confidence: 98%

Phagocytosis and Protein Processing Are Required for Presentation ofCryptococcus neoformansMitogen to T Lymphocytes

Syme

Spurrell

Ling³

et al. 2000

Infect Immun

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In addition to eliciting antigen specific T-cell-mediated immunity, Cryptococcus neoformans possesses a mitogen (CnM) that activates naive T cells to proliferate. This mechanism of T-cell activation is accessory cell dependent and major histocompatibility complex unrestricted. CnM-induced T-cell proliferation correlates with internalization of the organism, suggesting that intracellular processing is required to liberate CnM prior to presentation to T cells. To determine whether phagocytosis and processing are required, various inhibitors of accessory cell uptake and processing were used. C. neoformans was observed within the accessory cells. Paraformaldehyde fixation of the accessory cell abrogated presentation of CnM to T cells, indicating that a dynamic accessory cell surface was required. A lysosomotropic agent abrogated the response to CnM but had no effect on a control stimulus that did not require processing. Both aspartic acid and cysteine protease inhibitors blocked effective processing of CnM, so that it was unable to stimulate T cells. Finally, an inhibitor of microfilament polymerization abrogated proliferation to CnM. These results indicate that the mitogenic activity of C. neoformans requires phagocytosis of the organism, lysosomal or endosomal processing, proteolytic activity, and microfilament polymerization and intracellular transport as a prerequisite for T-cell proliferation.Cryptococcus neoformans is a pathogenic yeast that causes one of the leading fatal mycoses in AIDS (9,12,18,38). This clinical observation, in addition to animal studies, has made it clear that T-cell-mediated immunity is of paramount importance in host defense against C. neoformans (1,7,15,19,20,22,28,31). T-cell immunity is antigen specific; however, we have recently shown that T cells are also capable of responding to C. neoformans by an alternate mechanism of activation (36). Specifically, when T cells from a previously unexposed individual are placed in culture with C. neoformans, the organism induces a mitogenic response. The mitogenic T-cell response is accessory cell (AC) dependent but not major histocompatibility complex restricted (36). Since the whole organism is capable of mediating this mitogenic effect, it raises questions about how the C. neoformans mitogen (CnM) might be liberated or displayed prior to T-cell activation.We had previously shown that CnM was confined to the cell wall of the organism (32). Since CnM may be displayed on the cell wall, it is possible that it cross-links surface molecules on the T cell and AC analogous to superantigens. Alternately, the AC might produce an enzyme that results in extracellular degradation and release of CnM, with liberation of the molecule into the surrounding milieu, where it exerts its mitogenic effect. Finally, we considered the possibility that the organism must be taken up by the AC and degraded internally, with subsequent presentation of CnM by the AC to the T cell. We have previously shown that lymphocyte proliferation in response to C. neoformans correlate...

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Cell-mediated immunity in cryptococcosis

Cited by 114 publications

References 20 publications

Cryptococcus neoformansIs a Facultative Intracellular Pathogen in Murine Pulmonary Infection

Cryptococcus neoformansIs a Facultative Intracellular Pathogen in Murine Pulmonary Infection

Suppressor thymus-derived lymphocytes in fungal infection.

Phagocytosis and Protein Processing Are Required for Presentation ofCryptococcus neoformansMitogen to T Lymphocytes

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