Direct interactions of human natural killer cells with Cryptococcus neoformans inhibit granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha production

Murphy, Juneann W.; Zhou, Anqiang; Wong, Si Chai

doi:10.1128/iai.65.11.4564-4571.1997

Cited by 30 publications

(10 citation statements)

References 34 publications

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“…Similarly, various mucormycetes affect the IFN-γ release by human NK cells ( 64 ). In contrast, earlier studies report that C. neoformans downregulates of the production of GM-CSF and TNF-α in unstimulated human NK cells, as assessed by gene expression and supernatant protein levels ( 118 ).…”

Section: Interplay Of Nk Cells and Fungimentioning

confidence: 88%

Natural Killer Cells in Antifungal Immunity

2017

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Invasive fungal infections are still an important cause of morbidity and mortality in immunocompromised patients such as patients suffering from hematological malignancies or patients undergoing hematopoietic stem cell transplantion. In addition, other populations such as human immunodeficiency virus-patients are at higher risk for invasive fungal infection. Despite the availability of new antifungal compounds and better supportive care measures, the fatality rate of invasive fungal infection remained unacceptably high. It is therefore of major interest to improve our understanding of the host–pathogen interaction to develop new therapeutic approaches such as adoptive immunotherapy. As experimental methodologies have improved and we now better understand the complex network of the immune system, the insight in the interaction of the host with the fungus has significantly increased. It has become clear that host resistance to fungal infections is not only associated with strong innate immunity but that adaptive immunity (e.g., T cells) also plays an important role. The antifungal activity of natural killer (NK) cells has been underestimated for a long time. In vitro studies demonstrated that NK cells from murine and human origin are able to attack fungi of different genera and species. NK cells exhibit not only a direct antifungal activity via cytotoxic molecules but also an indirect antifungal activity via cytokines. However, it has been show that fungi exert immunosuppressive effects on NK cells. Whereas clinical data are scarce, animal models have clearly demonstrated that NK cells play an important role in the host response against invasive fungal infections. In this review, we summarize clinical data as well as results from in vitro and animal studies on the impact of NK cells on fungal pathogens.

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Section: Interplay Of Nk Cells and Fungimentioning

confidence: 88%

Natural Killer Cells in Antifungal Immunity

2017

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“…NK cells may further contribute to host defences by secreting IFN‐ γ and stimulating macrophages to kill the yeast (Kawakami et al , 2000). However, C. neoformans also decreases NK cell production of GM‐CSF and TNF‐ α , which has the potential to affect phagocyte activity and dampen the immune response (Murphy et al , 1997).…”

Section: Cryptococcus Neoformansmentioning

confidence: 99%

The immune response to fungal infections

2005

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SummaryDuring the past two decades, invasive fungal infections have emerged as a major threat to immunocompromised hosts. Patients with neoplastic diseases are at significant risk for such infections as a result of their underlying illness and its therapy. Aspergillus, Candida, Cryptococcus and emerging pathogens, such as the zygomycetes, dark walled fungi, Trichosporon and Fusarium, are largely opportunists, causing infection when host defences are breached. The immune response varies with respect to the fungal species and morphotype encountered. The risk for particular infections differs, depending upon which aspect of immunity is impaired. This article reviews the current understanding of the role and relative importance of innate and adaptive immunity to common and emerging fungal pathogens. An understanding of the host response to these organisms is important in decisions regarding use of currently available antifungal therapies and in the design of new therapeutic modalities.

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“…In contrast to the functions of TNF‐α and NO, IL‐10 inhibits the production of proinflammatory cytokines and seems to play a protective role in RA [30]. GXM increases secretion of IL‐10 and reduces the production of TNF‐α, IL‐1β, GM‐CSF and NO [8–10, 15, 16], as well as, decreasing the expression of class II MHC molecule and reduces proliferative T‐cell responses [11]. Furthermore, GXM diminishes TNF receptor expression [12] and is a potent inhibitor of leucocyte accumulation [5].…”

Section: Discussionmentioning

confidence: 99%

“…This compound binds to CD18 on human polymorphonuclear (PMN) cells, and has the potential to inhibit leucocyte infiltration into inflammatory sites [13]. GXM inhibits nitric oxide (NO) production by murine peritoneal macrophages [14] and inhibits production of granulocyte‐macrophage colony‐stimulating factor and TNF‐α production by human natural killer cells [15]. In vitro and in vivo investigations show that the inhibitory effects of capsular polysaccharides of culture filtrates of C. neoformans var.…”

Section: Introductionmentioning

confidence: 99%

Tolerability and Anti‐Inflammatory Effects of Glucuronoxylomannan in Collagen‐Induced Arthritis

et al. 2004

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This investigation was planned to assess the therapeutic efficacy of glucuronoxylomannan (GXM) in collagen-induced arthritis (CIA). GXM was isolated from culture filtrate of Cryptococcus neoformans var. gattii, serotype C. CIA was induced by the immunization of Dark Agouti rats with bovine type II collagen in incomplete Freund's adjuvant. GXM solution at two doses, 25 and 50 mg/kg, was administered intraperitoneally. Onset of i.p. injections of GXM to prevention and treatment groups was days 0 and 10 postimmunization, respectively. The WEHI-164 cell line was used for assaying tolerability, matrix metalloproteinase type 2 (MMP-2) activity and apoptosis. MMP-2 activity was assessed using zymography. For assessment of apoptosis, the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling method was used. The results of this experiment showed that the treatment of CIA with GXM at a dose of 50 mg/kg could suppress disease development both prophylactically and therapeutically. This beneficial effect of GXM was associated with a significant decrease in the anti-CII antibody response compared with untreated rats. Moreover, GXM therapy could diminish MMP-2 activity, but it had no notable effect on apoptosis. GXM also showed a high tolerability compared with certain steroidal and non-steroidal anti-inflammatory drugs. We conclude that GXM suppresses the development of disease in CIA and it could be recommended as a new immunosuppressive and anti-inflammatory agent for further investigations.

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Direct interactions of human natural killer cells with Cryptococcus neoformans inhibit granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha production

Cited by 30 publications

References 34 publications

Natural Killer Cells in Antifungal Immunity

Natural Killer Cells in Antifungal Immunity

The immune response to fungal infections

Tolerability and Anti‐Inflammatory Effects of Glucuronoxylomannan in Collagen‐Induced Arthritis

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