Plasmacytoid dendritic cells in skin lesions of classic Kaposi’s sarcoma

Abstract

Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), which allows them to provide anti-viral resistance and to link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer cells. pDCs are involved in the pathogenesis of several infectious [especially viral, such as Molluscum contagiosum (MC)], inflammatory/autoimmune, and neoplastic entities. Kaposi's sarcoma (KS) is a multifocal, systemic lympho-angioproliferative tumor associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Microscopy typically exhibits a chronic inflammatory lymphoplasmacytic infiltrate in addition to the vascular changes and spindle cell proliferation. Despite the extensive research done on the immune evasion strategies employed by KSHV, pDCs role in relation to KS has only rarely been investigated. Given this, we intend to investigate pDC occurrence and activity in the skin lesions of KS. Immunohistochemical staining for BDCA-2 (specific pDC marker) and MxA (surrogate marker for local type I IFN production) was performed on classic KS (n = 20) with the control group comprising inflamed MC (n = 20). As expected, BDCA-2+ pDCs were present in abundance with diffuse and intense MxA expression (indicative of local type I IFN production) in all inflamed MC cases (20 of 20, 100 %). Though present in all the KS cases, pDCs were significantly less abundant in KS than in inflamed MC cases, and MxA expression was patchy/weak in most KS cases. In summary, pDCs are part of the inflammatory host response in KS; however, they were generally low in number with decreased type I IFN production which is probably related to KSHV's ability to evade the immune system through the production of different viral proteins capable of suppressing IFN production as well as pDC function.

Distribution of Dendritic Cells in AIDS-Associated Oral Kaposi’s Sarcoma

“…Interestingly, plasmocytoid DC (pDC) has been the most studied subpopulation in Kaposi's sarcoma given its ability to recognize single-stranded RNA and unmethylated CpG motifs associated with viral infection, inducing an antiviral response within the host and a high production of interferon (25)(26)(27). Similar to our study, Stebbing et al (28) using HIV-1 infected patients, also showed a depletion of pDC in Kaposi's sarcoma patients compared with Kaposi's sarcoma-negative individuals, whereas Karouni et al (29) observed a significantly lower pDC count and a lower interferon production in classic kaposi's sarcoma than in mollusccum contagious cases. Although we did not correlate the distribution of LC and IDC observed in Kaposi's sarcoma patients with their respective CD4 count since this data were unavailable for consultation, potentially representing a limitation of our study, Grulich et al (30) stated that CD4 count could be an insensitive indicator of immune deficiency, because its count might not be an accurate or unbiased measure of immune function.…”

Designing a multi-epitope based vaccine to combat Kaposi Sarcoma utilizing immunoinformatics approach

“…As HHV-8 is a double stranded DNA virus, the Toll-Like Receptor-9 (TLR-9) expressed in the endoplasmic reticulum of Plasmacytoid dendritic cells should primarily recognize the structural components of the virus. There are several research articles which demonstrated the high levels of TLR-9 expression in HHV-8 infection 21–23 . The TLR-9 primarily express on the surface of plasmacytoid dendritic cells (pDCs) and B cells in humans.…”

CD123 immunoexpression in cutaneous lupus erythematosus, polymorphous light eruption, pityriasis rosea, and mycosis fungoides

“…PDC infiltration in vitiligo patients may be an early indicator of disease progression due to IFN-g production, and contact eczema has been detected anecdotally [25]. Besides, PDC infiltration was detected in pityriasis lichenoides [28], squamous cell carcinoma-keratoacanthoma [29], molluscum contagiosum [30], and Kaposi sarcoma [31]. Low PDC levels in patients with lupus erythematosus panniculitis (LEP) have been reported to reduce the response to treatment and be valuable in the prognosis of the disease [32].…”