Altered natural killer cells' response to herpes virus infection in multiple sclerosis involves KIR2DL2 expression

Rizzo, Roberta; Gentili, Valentina; Casetta, Ilaria; Caselli, Elisabetta; Gennaro, Riccardo De; Granieri, Enrico; Cassai, Enzo; Luca, Dario Di; Rotola, Antonella

doi:10.1016/j.jneuroim.2012.07.004

Cited by 48 publications

(71 citation statements)

References 60 publications

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“…Furthermore, a genetic background, namely specific KIR present on natural killer (NK) cells, has been shown to predispose to both susceptibility to herpesvirus infection and development of herpesvirus-associated diseases, such as type 2 diabetes and multiple sclerosis [6,23]. In fact, NK cells play an important role in eliminating virus-infected cells as well as tumor cells [8].…”

Section: Discussion/conclusionmentioning

confidence: 99%

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High prevalence of specific KIR types in patients with HHV-8 positive cutaneous vascular lesions: a possible predisposing factor?

et al. 2016

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Human herpesvirus 8 (HHV8) has been hypothesized to be a potential cofactor for the development of diverse cutaneous vascular proliferative lesions, including eruptive cherry angiomas. Recent reports evidenced the influence of killer cell immunoglobulin-like receptor (KIR) gene diversity in defining the susceptibility to symptomatic herpesvirus infections. In this study, skin samples from vascular lesions and healthy controls were characterized simultaneously for the presence of HHV8 and for the KIR genotype, focusing upon the presence of the KIR2DL2/DS2 and KIR2DL3 genes, which have been associated to herpesvirus susceptibility. The results showed that about 64 % of the vascular lesions resulted positive for the presence of HHV8, whereas no control healthy skin samples harbored HHV8 DNA. HHV8-positive patients had a significantly increased frequency of KIR2DL2/DS2 homozigosity and a concomitant decrease of the homozygous KIR2DL3 genotype, compared to healthy controls or HHV8-negative patients. Notably, the simultaneous presence of KIR2DL2/DS2 homozygosity and HHV8 infection resulted in a significantly increased risk to develop cutaneous lesions (OR 5.7) compared to the individual factors alone, suggesting that specific KIR genotypes might predispose to HHV8 symptomatic infection, allowing the virus to exert its angioproliferative activity at skin level.

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Section: Discussion/conclusionmentioning

confidence: 99%

“…In particular, the resistance to herpesvirus-associated diseases seems to be associated with the absence of KIR2DL2/DS2, whereas, conversely, a high prevalence of KIR2DL2 is associated to an increased risk [6,23].…”

Section: Introductionmentioning

confidence: 97%

High prevalence of specific KIR types in patients with HHV-8 positive cutaneous vascular lesions: a possible predisposing factor?

et al. 2016

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“…In parallel, individual susceptibility might be important for the development of the disease. We recently reported that specific Killer Inhibitory Receptors (KIR) present on NK cells are related to a decreased ability to control herpesviruses infection [24], and it may be hypothesized that individuals with an immune response not capable of controlling infectious replication might be more susceptible to infection-related tumor development.…”

Section: Discussionmentioning

confidence: 99%

Detection of Chlamydophila pneumoniae and human herpesvirus 8 in primary cutaneous anaplastic large-cell lymphoma: a case report

Borghi

Caselli

Luca

et al. 2013

Infect Agents Cancer

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BackgroundThe etiology of primary cutaneous anaplastic large-cell CD30+ lymphoma is largely unknown, and although an infectious involvement has been suspected, the implication of infectious agents in its pathogenesis is still unclear.FindingsWe report the case of a HIV-negative patient referred to our hospital with a rapidly enlarging skin tumor on her upper eyelid. Surgical excision was performed and histological analysis evidenced a primary cutaneous anaplastic large-cell lymphoma. Due to the ocular localization and to the prominent angiogenic component of the lesion, molecular analyses for the detection of Chlamydophila pneumoniae and HHV8 were performed, revealing the presence of an infection by both pathogens in surgical biopsy and in peripheral blood mononuclear cells.ConclusionsThese findings suggest for the first time a possible association of C. pneumoniae and/or HHV8 infection, or both together, with primary cutaneous anaplastic large-cell lymphoma in non-immunocompromised and HIV-negative subjects. This potential pathogenic association, if confirmed, could provide potential indications for future therapy.

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“…Activation of TLR2 is followed by the production of inflammatory cytokines, including IL-6, IL-8, and TNF- α . In addition, the induction of IFN- α by HSV involves TLR9 [66]. …”

Section: Role Of Innate Immunity In the Pathology Of Multiple Sclementioning

confidence: 99%

“…NLR proteins NLRP3, NLRP1, and NLRC4 as well as a recently identified HIN-200 protein absent in melanoma 2 (AIM2) are activated by pathogen- and danger-associated molecular patterns (PAMPs and DAMPs, resp.) results in the recruitment of the inflammasome-adaptor protein, ASC (also known as PYCARD), and procaspase-1 [66]. …”

Section: Nod-like Receptor and Regulation On Multiple Sclerosismentioning

confidence: 99%

Initial Immunopathogenesis of Multiple Sclerosis: Innate Immune Response

Hernández‐Pedro

Espinosa-Ramirez

Cruz

et al. 2013

Clinical and Developmental Immunology

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Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The hallmark to MS is the demyelinated plaque, which consists of a well-demarcated hypocellular area characterized by the loss of myelin, the formation of astrocytic scars, and the mononuclear cell infiltrates concentrated in perivascular spaces composed of T cells, B lymphocytes, plasma cells, and macrophages. Activation of resident cells initiates an inflammatory cascade, leading to tissue destruction, demyelination, and neurological deficit. The immunological phenomena that lead to the activation of autoreactive T cells to myelin sheath components are the result of multiple and complex interactions between environment and genetic background conferring individual susceptibility. Within the CNS, an increase of TLR expression during MS is observed, even in the absence of any apparent microbial involvement. In the present review, we focus on the role of the innate immune system, the first line of defense of the organism, as promoter and mediator of cross reactions that generate molecular mimicry triggering the inflammatory response through an adaptive cytotoxic response in MS.

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Altered natural killer cells' response to herpes virus infection in multiple sclerosis involves KIR2DL2 expression

Cited by 48 publications

References 60 publications

High prevalence of specific KIR types in patients with HHV-8 positive cutaneous vascular lesions: a possible predisposing factor?

High prevalence of specific KIR types in patients with HHV-8 positive cutaneous vascular lesions: a possible predisposing factor?

Detection of Chlamydophila pneumoniae and human herpesvirus 8 in primary cutaneous anaplastic large-cell lymphoma: a case report

Initial Immunopathogenesis of Multiple Sclerosis: Innate Immune Response

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