Dendritic cells: key players in human herpesvirus 8 infection and pathogenesis

Campbell, Diana; Rappocciolo, Giovanna; Jenkins, Frank J.; Rinaldo, Charles R.

doi:10.3389/fmicb.2014.00452

Cited by 27 publications

(24 citation statements)

References 118 publications

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“…22 Dendritic cells play an important role in HHV8 infection and pathogenesis. 23,24 Myeloid-dendritic cells and macrophages can be infected by HHV8 through DC-SIGN receptor 25 and follicular dendriticlike cells have shown to express DC-SIGN. 26…”

Section: Discussionmentioning

confidence: 99%

HHV8-related lymphoid proliferations: a broad spectrum of lesions from reactive lymphoid hyperplasia to overt lymphoma

et al. 2017

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Human herpesvirus 8 (HHV8)-associated lymphoid proliferations are uncommon and poorly characterized disorders mainly affecting immunosuppressed patients, especially with HIV infection. They encompass different diseases with overlapping features that complicate their classification. In addition, the role of HHV8 in reactive lymphoid hyperplasia is not well known. To analyze the clinicopathological spectrum of these lesions, we have reviewed 66 biopsies of 61 patients with HHV8 infection. All cases were also investigated for Epstein-Barr virus (EBV) and HIV infection. We identified 13 (20%) cases of HHV8-related reactive lymphoid hyperplasia, 2 (3%) HHV8 plasmablastic proliferations of the splenic red pulp, 28 (42%) multicentric Castleman disease, 6 (9%) germinotropic lymphoproliferative disorders, and 17 (26%) HHV8-related lymphomas. As expected, the pathologic subtype was predictive of overall survival (P<0.05). Forty-seven of our cases were HIV positive (77%). In addition to the classical presentation of the different entities, we identified novel and overlapping features. Reactive HHV8 proliferations were frequently associated with systemic symptoms but never progressed to overt HHV8-positive lymphoma. Two cases had a plasmablastic proliferation limited to spleen. Eight cases of multicentric Castleman disease had a previously unrecognized presentation shortly after the diagnosis of HIV infection, six cases had cavity effusions, and three showed plasmablast enriched proliferations. One germinotropic lymphoproliferative disorder was EBV negative and three occurred in HIV-positive patients, who had distinctive clinical and morphological features. Two of the HHV8-related lymphomas did not fulfill the criteria for previously recognized entities. All these findings expand the clinical and pathological spectrum of HHV8-related lymphoid proliferations, which is broader than current recognized.

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Section: Discussionmentioning

confidence: 99%

HHV8-related lymphoid proliferations: a broad spectrum of lesions from reactive lymphoid hyperplasia to overt lymphoma

et al. 2017

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“…This agrees with a previous study from our laboratory reporting that HHV-8 skews the cytokine response of infected dendritic cells to a Th2 response. 19,20 The cytokine profile of HHV-8 seropositive men (among the cancer controls) represents a pro-inflammatory without killing immune response, which is favorable for maintenance of viral latency.…”

Section: Discussionmentioning

confidence: 99%

Human herpesvirus 8 infection contributes to a T helper 2 immune response in men from Tobago with prostate cancer

et al. 2016

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Abbreviations & Acronyms BMI = body mass index BPH = benign prostatic hyperplasia CRP = C-reactive protein DRE = digital rectal examination HHV-8 = human herpesvirus 8 IFNc = interferon gamma IL = interleukin MDSC = myeloid-derived suppressor cells PSA = prostate-specific antigen Th2 = T helper 2 TNF-a = tumor necrosis factor alpha Objectives: To compare the cytokine profile between human herpesvirus 8 seropositive and seronegative men with and without prostate cancer. Methods: The study sample was obtained from the Tobago Prostate Survey, an ongoing study of prostate cancer in the Caribbean island of Tobago. Participants in the study were recruited mostly by public service announcement and by word of mouth. For analyses of circulating levels of pro-inflammatory cytokines, participants with biopsyconfirmed prostate cancer (n = 79) were compared with control participants (n = 87). Results: Cytokine analyses showed a T helper 2 response with suppressed T helper 1 response in prostate cancer patients, as evidenced by significantly increased levels of interleukin-13 and reduced levels of interleukin-12p70. Herpesvirus 8 seropositive men showed significantly increased levels of interleukin-13 and interleukin-10. At logistic regression analyses, interleukin-12p70 predicted prostate cancer in 94.4% of human herpesvirus 8 seropositive men. Conclusions: These findings show that prostate cancer elicits an antitumor, T helper 2 response with a suppressed T helper 1 response. Human herpesvirus 8 infection results in a similar immune response supporting the hypothesis that in Tobago, human herpesvirus 8 establishes a chronic infection that can contribute to an immune response favoring the formation and survival of prostate cancer.

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“…37,38 Previous studies by ours and other's laboratories have reported that KSHV infects DCs or their monocyte precursors in vivo 40 or in vitro, resulting in a reduction of their immune functions or in an inhibition of monocyte differentiation. [41][42][43][44][45][46] In this study, we investigated whether KSHV infection of THP-1 monocytoid cells or primary monocytes could interfere with their autophagic process induced by several stimuli and be the underlying mechanism leading to their impaired in vitro differentiation.…”

Section: Introductionmentioning

confidence: 99%

KSHV reduces autophagy in THP-1 cells and in differentiating monocytes by decreasing CAST/calpastatin and ATG5 expression

et al. 2016

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We have previously shown that Kaposi sarcoma-associated herpesvirus (KSHV) impairs monocyte differentiation into dendritic cells (DCs). Macroautophagy/autophagy has been reported to be essential in such a differentiating process. Here we extended these studies and found that the impairment of DC formation by KSHV occurs through autophagy inhibition. KSHV indeed reduces CAST (calpastatin) and consequently decreases ATG5 expression in both THP-1 monocytoid cells and primary monocytes. We unveiled a new mechanism put in place by KSHV to escape from immune control. The discovery of viral immune suppressive strategies that contribute to the onset and progression of viral-associated malignancies is of fundamental importance for finding new therapeutic approaches against them.

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Dendritic cells: key players in human herpesvirus 8 infection and pathogenesis

Cited by 27 publications

References 118 publications

HHV8-related lymphoid proliferations: a broad spectrum of lesions from reactive lymphoid hyperplasia to overt lymphoma

HHV8-related lymphoid proliferations: a broad spectrum of lesions from reactive lymphoid hyperplasia to overt lymphoma

Human herpesvirus 8 infection contributes to a T helper 2 immune response in men from Tobago with prostate cancer

KSHV reduces autophagy in THP-1 cells and in differentiating monocytes by decreasing CAST/calpastatin and ATG5 expression

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