Natural Killer Cells and Antifungal Host Response

Schmidt, Stanislaw; Zimmermann, Stefanie‐Yvonne; Tramsen, Lars; Koehl, Ulrike; Lehrnbecher, Thomas

doi:10.1128/cvi.00606-12

Cited by 51 publications

(55 citation statements)

References 88 publications

(99 reference statements)

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“…Natural killer (NK) cells bind and inhibit C. neoformans growth in vitro [94] and induce fungal clearance in mice [95]. Human NK cells are able to kill C. neoformans [96] with direct killing being mediated by perforin [97,98].…”

Section: Innate Immune and Cellular Responses To C Neoformansmentioning

confidence: 99%

Host Immunity to Cryptococcus Neoformans

2015

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Cryptococcosis is caused by the fungal genus Cryptococcus. Cryptococcosis, predominantly meningoencephalitis, emerged with the HIV pandemic, primarily afflicting HIV-infected patients with profound T-cell deficiency. Where in use, combination antiretroviral therapy has markedly reduced the incidence of and risk for disease, but cryptococcosis continues to afflict those without access to therapy, particularly in sub-Saharan Africa and Asia. However, cryptococcosis also occurs in solid organ transplant recipients and patients with other immunodeficiencies as well as those with no known immunodeficiency. This article reviews innate and adaptive immune responses to C. neoformans, with an emphasis on recent studies on the role of B cells, natural IgM and Fc gamma receptor polymorphisms in resistance to cryptococcosis.

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Section: Innate Immune and Cellular Responses To C Neoformansmentioning

confidence: 99%

Host Immunity to Cryptococcus Neoformans

2015

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“…NK cells are involved in the immune surveillance of tumours and microbes, such as viruses, fungi, intracytoplasmic bacteria and parasites [4][5][6] . Despite their classification as innate lymphocytes, it is becoming clear that NK cells also have adaptive features, including some memory properties in particular 7,8 .…”

mentioning

confidence: 99%

SHP-1-mediated inhibitory signals promote responsiveness and anti-tumour functions of natural killer cells

et al. 2014

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Natural killer (NK) cells are cytotoxic innate lymphoid cells that are involved in immune defense. NK cell reactivity is controlled in part by MHC class I recognition by inhibitory receptors, but the underlying molecular mechanisms remain undefined. Using a mouse model of conditional deletion in NK cells, we show here that the protein tyrosine phosphatase SHP-1 is essential for the inhibitory function of NK cell MHC class I receptors. In the absence of SHP-1, NK cells are hyporesponsive to tumour cells in vitro and their early Ca 2 þ signals are compromised. Mice without SHP-1 in NK cells are unable to reject MHC class I-deficient transplants and to control tumours in vivo. Thus, the inhibitory activity of SHP-1 is needed for setting the threshold of NK cell reactivity.

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“…Importantly, reduced surface expression of major histocompatibility complex (MHC) class I on a cell is known to activate NK cells, a cell type of the innate branch of the immune system (21,22), a phenomenon known as "missing self" recognition (23). NK cells constitute the first line of defense against pathogens such as viruses, fungi, and bacteria but also against transformed cells (24)(25)(26)(27)(28). Their activity is controlled by a balance of signals mediated by activating and inhibitory receptors (29).…”

mentioning

confidence: 99%

Human Herpesvirus 6B Downregulates Expression of Activating Ligands during Lytic Infection To Escape Elimination by Natural Killer Cells

Schmiedel

Tai

Levi‐Schaffer

et al. 2016

J Virol

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The Herpesviridae family consists of eight viruses, most of which infect a majority of the human population. One of the lessstudied members is human herpesvirus 6 (HHV-6) (Roseolovirus), which causes a mild, well-characterized childhood disease. Primary HHV-6 infection is followed by lifelong latency. Reactivation frequently occurs in immunocompromised patients, such as those suffering from HIV infection or cancer or following transplantation, and causes potentially life-threatening complications. In this study, we investigated the mechanisms that HHV-6 utilizes to remain undetected by natural killer (NK) cells, which are key participants in the innate immune response to infections. We revealed viral mechanisms which downregulate ligands for two powerful activating NK cell receptors: ULBP1, ULBP3, and MICB, which trigger NKG2D, and B7-H6, which activates NKp30. Accordingly, this downregulation impaired the ability of NK cells to recognize HHV-6-infected cells. Thus, we describe for the first time immune evasion mechanisms of HHV-6 that protect lytically infected cells from NK elimination. IMPORTANCEHuman herpesvirus 6 (HHV-6) latently infects a large portion of the human population and can reactivate in humans lacking a functional immune system, such as cancer or AIDS patients. Under these conditions, it can cause life-threatening diseases. To date, the actions and interplay of immune cells, and particularly cells of the innate immune system, during HHV-6 infection are poorly defined. In this study, we aimed to understand how cells undergoing lytic HHV-6 infection interact with natural killer (NK) cells, innate lymphocytes constituting the first line of defense against viral intruders. We show that HHV-6 suppresses the expression of surface proteins that alert the immune cells by triggering two major receptors on NK cells, NKG2D and NKp30. As a consequence, HHV-6 can replicate undetected by the innate immune system and potentially spread infection throughout the body. This study advances the understanding of HHV-6 biology and the measures it uses to successfully escape immune elimination. Human herpesvirus 6 (HHV-6) (Roseolovirus) was long neglected in research and medical diagnostics; however, in the past few years, it gained increasing attention. A variety of clinical complications were found to be associated with HHV-6 infection, especially concerning immunocompromised patients, in whom it has the ability to cause severe morbidity and mortality (1, 2). HHV-6 is subclassified into two distinct variants, HHV-6A and HHV-6B, which are considered independent viruses but share major genome sequence homologies and epidemiologies (3,4). Similarly to other members of the herpesvirus family, HHV-6 causes a relatively short and mild primary disease called roseola infantum, usually in children up to the age of 2 years, with a sudden rise of fever and rash as major symptoms (5). Following this initial infection, HHV-6 establishes lifelong latency in about 90% of all individuals examined (2). Reactivation frequentl...

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Natural Killer Cells and Antifungal Host Response

Cited by 51 publications

References 88 publications

Host Immunity to Cryptococcus Neoformans

Host Immunity to Cryptococcus Neoformans

SHP-1-mediated inhibitory signals promote responsiveness and anti-tumour functions of natural killer cells

Human Herpesvirus 6B Downregulates Expression of Activating Ligands during Lytic Infection To Escape Elimination by Natural Killer Cells

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