Anti-Cryptococcus neoformans antibodies during cryptococcosis in patients with the acquired immunodeficiency syndrome

Dromer, Françoise; Denning, David W.; Stevens, David A.; Noble, A.; Hamilton, John R.

doi:10.1016/0888-0786(96)87297-0

Cited by 8 publications

(4 citation statements)

References 31 publications

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“…Remarkably, anti-cryptococcal IgM and IgG antibodies were detected in considerably high frequencies even in sera from healthy human individuals, which we categorize as "preexisting" antibodies. This finding is in accordance with previously published results, demonstrating the presence of antibodies directed against cryptococcal CPS (33,(47)(48)(49)(50)(51)(52)(53)(54)56), cryptococcal proteins (58)(59)(60)(61)(62) or mannoproteins (57) in human sera, independent of cryptococcal disease or the HIV status.…”

Section: Discussionsupporting

confidence: 93%

“…proper immune response to cryptococcal infection, and, therefore, no increase in anti-cryptococcal IgG titers is detectable in these patients. However, some studies measured increased anti-GXM IgG titers in HIV-positive patients with or without cryptococcal infection compared to HIV-negative individuals (49,50,52,53,56). This might be caused by underlying HIV infection leading to increased levels of serum IgG in general (77)(78)(79).…”

Section: Discussionmentioning

confidence: 99%

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Identification of Disease-Associated Cryptococcal Proteins Reactive With Serum IgG From Cryptococcal Meningitis Patients

et al. 2021

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Cryptococcus neoformans, an opportunistic fungal pathogen ubiquitously present in the environment, causes cryptococcal meningitis (CM) mainly in immunocompromised patients, such as AIDS patients. We aimed to identify disease-associated cryptococcal protein antigens targeted by the human humoral immune response. Therefore, we used sera from Colombian CM patients, with or without HIV infection, and from healthy individuals living in the same region. Serological analysis revealed increased titers of anti-cryptococcal IgG in HIV-negative CM patients, but not HIV-positive CM patients, compared to healthy controls. In contrast, titers of anti-cryptococcal IgM were not affected by CM. Furthermore, we detected pre-existing IgG and IgM antibodies even in sera from healthy individuals. The observed induction of anti-cryptococcal IgG but not IgM during CM was supported by analysis of sera from C. neoformans-infected mice. Stronger increase in IgG was found in wild type mice with high lung fungal burden compared to IL-4Rα-deficient mice showing low lung fungal burden. To identify the proteins targeted by human anti-cryptococcal IgG antibodies, we applied a quantitative 2D immunoproteome approach identifying cryptococcal protein spots preferentially recognized by sera from CM patients or healthy individuals followed by mass spectrometry analysis. Twenty-three cryptococcal proteins were recombinantly expressed and confirmed to be immunoreactive with human sera. Fourteen of them were newly described as immunoreactive proteins. Twelve proteins were classified as disease-associated antigens, based on significantly stronger immunoreactivity with sera from CM patients compared to healthy individuals. The proteins identified in our screen significantly expand the pool of cryptococcal proteins with potential for (i) development of novel anti-cryptococcal agents based on implications in cryptococcal virulence or survival, or (ii) development of an anti-cryptococcal vaccine, as several candidates lack homology to human proteins and are localized extracellularly. Furthermore, this study defines pre-existing anti-cryptococcal immunoreactivity in healthy individuals at a molecular level, identifying target antigens recognized by sera from healthy control persons.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Identification of Disease-Associated Cryptococcal Proteins Reactive With Serum IgG From Cryptococcal Meningitis Patients

et al. 2021

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“…Studies have shown that AIDS patients generate less anti- C. neoformans antibody than healthy patients, and the severe prognosis for cryptococcosis in AIDS patients may be linked to this defect (Subramaniam et al, 2009). Antibodies generated by infected AIDS patients may be less protective against C. neoformans infection, produced at titers too low for effective opsonization, or production could be critically delayed early in infection (Dromer et al, 1988; Dromer et al, 1995). It is thus possible that yeast evasion of phagocytosis by macrophages plays an important role in the development of cryptococcosis in immunocompromised individuals.…”

Section: Introductionmentioning

confidence: 99%

A Major Role for Capsule-Independent Phagocytosis-Inhibitory Mechanisms in Mammalian Infection by Cryptococcus neoformans

Chun

Brown

Madhani

2011

Cell Host & Microbe

104

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Summary The anti-phagocytic polysaccharide capsule of the human fungal pathogen Cryptococcus neoformans is a major virulence attribute. However, previous studies of the pleiotropic virulence determinant Gat201, a GATA-family transcription factor, suggested that capsule-independent antiphagocytic mechanisms exist. We have determined that Gat201 controls the mRNA levels of ~1100 genes (16% of the genome) and binds the upstream regions of ~130 genes. Seven Gat201-bound genes encode for putative and known transcription factors—including two previously implicated in virulence—suggesting an extensive regulatory network. Systematic analysis pinpointed two critical Gat201-bound genes, GAT204 (a transcription factor) and BLP1, which account for much of the capsule-independent antiphagocytic function of Gat201. A strong correlation was observed between the quantitative effects of single and double mutants on phagocytosis in vitro and on host colonization in vivo. This genetic dissection provides evidence that capsule-independent anti-phagocytic mechanisms are pivotal for successful mammalian infection by C. neoformans.

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“…This would imply that the inhibitory factor(s) in CSF is insufficient by itself to arrest the disease. However, we [7] and others have shown infection with the ubiquitous organism C. neoformans is common (80% of normal subjects have antibodies), yet central nervous system (CNS) disease is rare. It may be that the CSF inhibitory factor(s) contributes to defence of the CNS under ordinary circumstances, but is insufficient in others, such as when other host defences are compromised or fungemia is heavy.…”

Section: Discussionmentioning

confidence: 99%

Antifungal activity of cerebrospinal fluid against Cryptococcus neoformans and Candida species

et al. 2008

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The effect of human cerebrospinal fluid (CSF) on the growth of Cryptococcus neoformans and Candida species was tested in RPMI‐1640. CSF alone was highly fungistatic for both yeasts and inhibited growth in a concentration‐dependent manner. Unlike human serum, CSF did not collaborate with fluconazole for killing C. neoformans. Molecular sieve fractionation of CSF on a G‐200 Sephadex column yielded a highly antifungal fraction with a molecular weight around 66 kDa. On SDS‐PAGE this fraction migrated as a major and a minor band corresponding to the mobility of bovine serum albumin. These novel findings suggest that CSF contains a factor(s) that provides resistance to the growth of C. neoformans or Candida species.

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Anti-Cryptococcus neoformans antibodies during cryptococcosis in patients with the acquired immunodeficiency syndrome

Cited by 8 publications

References 31 publications

Identification of Disease-Associated Cryptococcal Proteins Reactive With Serum IgG From Cryptococcal Meningitis Patients

Identification of Disease-Associated Cryptococcal Proteins Reactive With Serum IgG From Cryptococcal Meningitis Patients

A Major Role for Capsule-Independent Phagocytosis-Inhibitory Mechanisms in Mammalian Infection by Cryptococcus neoformans

Antifungal activity of cerebrospinal fluid against Cryptococcus neoformans and Candida species

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