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.
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Abbas O, Hussein L, Kurban M, Kibbi AG (2014) Plasmacytoid dendritic cell involvement in the host response against keratoacanthoma. J Am Acad Dermatol 70:1142–1145
Abou Rahal J, Kurban M, Kibbi AG, Abbas O (2016) Plasmacytoid dendritic cells in alopecia areata: missing link? J Eur Acad Dermatol Venereol 30:119–123
Bluth MJ, Zaba LC, Moussai D, Suárez-Fariñas M, Kaporis H, Fan L, Pierson KC, White TR, Pitts-Kiefer A, Fuentes-Duculan J, Guttman-Yassky E, Krueger JG, Lowes MA, Carucci JA (2009) Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor stimulators of T-cell proliferation. J Invest Dermatol 129:2451–2462
Butler LM, Jeffery HC, Wheat RL, Rae PC, Townsend K, Alkharsah KR, Schulz TF, Nash GB, Blackbourn DJ (2011) Kaposi’s sarcoma-associated herpesvirus infection of endothelial cells inhibits neutrophil recruitment through an interleukin-6-dependent mechanism: a new paradigm for viral immune evasion. J Virol 85:7321–7332
Charles J, Chaperot L, Salameire D, Di Domizio J, Aspord C, Gressin R, Jacob MC, Richard MJ, Beani JC, Plumas J, Leccia MT (2010) Plasmacytoid dendritic cells and dermatological disorders: focus on their role in autoimmunity and cancer. Eur J Dermatol 20(1):16–23
Célestin Schartz NE, Chevret S, Paz C, Kerob D, Verola O, Morel P, Lebbé C (2008) Imiquimod 5% cream for treatment of HIV-negative Kaposi’s sarcoma skin lesions: a phase I to II, open-label trial in 17 patients. J Am Acad Dermatol 58:585–591
Della Bella S, Nicola S, Brambilla L, Riva A, Ferrucci S, Presicce P, Boneschi V, Berti E, Villa ML (2006) Quantitative and functional defects of dendritic cells in classic Kaposi’s sarcoma. Clin Immunol 119:317–329
Gilliet M, Cao W, Liu YJ (2008) Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat Rev Immunol 8:594–606
Guttman-Yassky E, Kra-Oz Z, Cohen A, Sattinger Y, Rot T, Sarid R, Bergman R (2006) Rapidly progressive classic Kaposi sarcoma in an adolescent: response to interferon alfa therapy and biological correlates. Br J Dermatol 154:555–557
Hartmann E, Wollenberg B, Rothenfusser S, Wagner M, Wellisch D, Mack B, Giese T, Gires O, Endres S, Hartmann G (2003) Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer. Cancer Res 63:6478–6487
Jacobs SR, Damania B (2011) The viral interferon regulatory factors of KSHV: immunosuppressors or oncogenes? Front Immunol 2:19
Joo CH, Shin YC, Gack M, Wu L, Levy D, Jung JU (2007) Inhibition of interferon regulatory factor 7 (IRF7)-mediated interferon signal transduction by the Kaposi’s sarcoma-associated herpesvirus viral IRF homolog vIRF3. J Virol 81:8282–8292
Lee HR, Brulois K, Wong L, Jung JU (2012) Modulation of immune system by Kaposi’s sarcoma-associated herpesvirus: lessons from viral evasion strategies. Front Microbiol 3:44
Saadeh D, Kurban M, Kibbi AG, Abbas O (2014) Involvement of plasmacytoid dendritic cells in the immunological response against Orf infection. JAMA Dermatol 150:1112–1113
Schwartz RA, Micali G, Nasca MR, Scuderi L (2008) Kaposi sarcoma: a continuing conundrum. J Am Acad Dermatol 59:179–206
Sleiman R, Kurban M, Abbas O (2015) Evaluation of the diagnostic value of plasmacytoid dendritic cells in differentiating the lymphocytic cicatricial alopecias. Dermatology 231:158–163
Takaoka A, Tamura T, Taniguchi T (2008) Interferon regulatory factor family of transcription factors and regulation of oncogenesis. Cancer Sci 99:467–478
Vermi W, Fisogni S, Salogni L, Schärer L, Kutzner H, Sozzani S, Lonardi S, Rossini C, Calzavara-Pinton P, LeBoit PE, Facchetti F (2011) Spontaneous regression of highly immunogenic Molluscum contagiosum virus (MCV)-induced skin lesions is associated with plasmacytoid dendritic cells and IFN-DC infiltration. J Invest Dermatol 131:426–434
Vermi W, Soncini M, Melocchi L, Sozzani S, Facchetti F (2011) Plasmacytoid dendritic cells and cancer. J Leukoc Biol 90:681–690
West JA, Gregory SM, Sivaraman V, Su L, Damania B (2011) Activation of plasmacytoid dendritic cells by Kaposi’s sarcoma-associated herpesvirus. J Virol 85:895–904
Wies E, Hahn AS, Schmidt K, Viebahn C, Rohland N, Lux A, Schellhorn T, Holzer A, Jung JU, Neipel F (2009) The Kaposi’s sarcoma-associated herpesvirus-encoded vIRF-3 inhibits cellular IRF-5. J Biol Chem 284:8525–8538
Yu Y, Hayward GS (2010) The ubiquitin E3 ligase RAUL negatively regulates type i interferon through ubiquitination of the transcription factors IRF7 and IRF3. Immunity 33:863–877
Yu Y, Wang SE, Hayward GS (2005) The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation. Immunity 22:59–70
Zhu FX, King SM, Smith EJ, Levy DE, Yuan Y (2002) A Kaposi’s sarcoma-associated herpesviral protein inhibits virus-mediated induction of type I interferon by blocking IRF-7 phosphorylation and nuclear accumulation. Proc Natl Acad Sci USA 99:5573–5578
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Karouni, M., Kurban, M. & Abbas, O. Plasmacytoid dendritic cells in skin lesions of classic Kaposi’s sarcoma. Arch Dermatol Res 308, 487–492 (2016). https://doi.org/10.1007/s00403-016-1671-6
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DOI: https://doi.org/10.1007/s00403-016-1671-6