Fungal infections in nontransplant patients with hematologic malignancies

Segal, Brahm H.; Bow, Eric J.; Menichetti, F.

doi:10.1016/s0891-5520(02)00043-0

Cited by 60 publications

(43 citation statements)

References 128 publications

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“…Under normal conditions Candida is not pathogenic, but suppressed immunity or mucosal damage can lead to local or disseminated infections, the latter being associated with a high mortality (1). Neutrophils (polymorphonuclear neutrophils [PMNs]) play an important role in the host defense against C. albicans, and neutropenia poses a strong risk factor in the development of disseminated candidiasis (2,3).…”

mentioning

confidence: 99%

Neutrophil-Mediated Inhibition of Proinflammatory Cytokine Responses

Gresnigt

Joosten

Verschueren

et al. 2012

The Journal of Immunology

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Neutrophils (polymorphonuclear neutrophils [PMNs]) play an elaborate role in the innate immune response against invading pathogens. Recent research provided evidence that PMNs can play a modulatory role in inflammation next to their primary role of phagocytosis. In the current study, we investigated whether neutrophils can modulate the innate immune response against Candida albicans. Production of the proinflammatory cytokines IL-1β and TNF-α by human PBMCs in response to C. albicans or LPS was decreased by coculture of PMNs; however, the anti-inflammatory cytokine IL-10 remained unaffected. Using Transwells and cells of patients with chronic granulomatous disease, we show that this downregulation of proinflammatory cytokine production was independent of phagocytosis and reactive oxygen species but was dependent on a soluble factor. We suggest that neutrophil-derived proteases are responsible for the downregulation of IL-1β and TNF-α, as cytokine production could be recovered by addition of α1-antitrypsin, an endogenous inhibitor of serine proteases. PMN lysates and neutrophil elastase could degrade recombinant human IL-1β and TNF-α but not IL-10, and this could be inhibited by addition of α1-antitrypsin. Moreover, we also provide evidence that the dampening effect of PMNs is present in vivo in a murine zymosan-induced arthritis model and a murine experimental endotoxemia model. Altogether, our data show that PMNs can dampen the proinflammatory response to C. albicans by protease-mediated degradation of cytokines. This observation suggest that PMNs might play a important regulatory role in the host defense against C. albicans and can be important for understanding the regulation of inflammation in general.

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confidence: 99%

Neutrophil-Mediated Inhibition of Proinflammatory Cytokine Responses

Gresnigt

Joosten

Verschueren

et al. 2012

The Journal of Immunology

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“…May progress rapidly; mortality in excess of 80% in disseminated disease. Scedosporium (76) (83) Can cause skin or pulmonary involvement. Associated with high mortality.…”

Section: Aspergillus Sp(77)(78)(74)(79)mentioning

confidence: 99%

Infections in Leukemia

Chandran¹,

Hakki²,

Spurgeon³

2012

Sepsis - An Ongoing and Significant Challenge

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“…Although it is ubiquitous in the environment and primary C. neoformans infection is acquired in childhood (1,26,61), cryptococcal disease (cryptococcosis) occurs predominantly in immunocompromised hosts (10), such as patients with AIDS (64) or hematological malignancies (49,56), patients receiving chemotherapy for malignancy (45) or immunosuppressive agents for organ transplantation (29,63), and those with underlying metabolic disorders (14,32). Recently, it has come to light that, in addition to occurring in the setting of immunosuppression, cryptococcosis also can stem from an exuberant immune response (11,19), such as that seen after immune reconstitution in AIDS patients on antiretroviral therapy (30) and in solid-organ transplant recipients (59).…”

mentioning

confidence: 99%

Therapeutic Efficacy of a Conjugate Vaccine Containing a Peptide Mimotope of Cryptococcal Capsular Polysaccharide Glucuronoxylomannan

Datta¹,

Lees

Pirofski

2008

Clin Vaccine Immunol

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Vaccination with P13, a peptide mimotope of the cryptococcal capsular polysaccharide glucuronoxylomannan (GXM), has been shown to confer protection against a subsequent lethal Cryptococcus neoformans challenge. In this study, we sought to investigate whether P13-based vaccines could be effective in an alreadyestablished infection. To address this question, we developed a systemic chronic cryptococcal infection model. We vaccinated chronically infected mice with P13-protein conjugates and monitored their survival. Compared to the controls, the conjugates prolonged the survival of chronically infected mice. The degree of protection was a function of the mouse strain (BALB/c or C57BL/6), the carrier protein (tetanus toxoid or diphtheria toxoid), and the route of infection (intraperitoneal or intravenous). Serum GXM levels were correlated with the day of death, but the correlation was driven by the carrier protein and mouse strain.

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Fungal infections in nontransplant patients with hematologic malignancies

Cited by 60 publications

References 128 publications

Neutrophil-Mediated Inhibition of Proinflammatory Cytokine Responses

Neutrophil-Mediated Inhibition of Proinflammatory Cytokine Responses

Infections in Leukemia

Therapeutic Efficacy of a Conjugate Vaccine Containing a Peptide Mimotope of Cryptococcal Capsular Polysaccharide Glucuronoxylomannan

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