Toll-Like Receptors 7, 8, and 9 Expression and Function in Primary Human Cervical Cancer Langerhans Cells Evidence of Anergy
| Autor: | Surya Ramachandran, Mahesh M. Kumar, Sreenivas Adurthi, H. Krishnamurthy, Omana Joy, UD Bafna, R. S. Jayshree, Devi K. Uma, Geetashree Mukherjee, Sudhir Krishna |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
medicine.medical_treatment Primary Cell Culture Uterine Cervical Neoplasms Biology Ligands Biochemistry Immune tolerance Interferon medicine Tumor Cells Cultured Humans Acute monocytic leukemia Aged Clonal Anergy Obstetrics and Gynecology TLR9 Interleukin Middle Aged medicine.disease Gene Expression Regulation Neoplastic Cytokine Oncology Toll-Like Receptor 7 Cell culture Toll-Like Receptor 8 Case-Control Studies Langerhans Cells Toll-Like Receptor 9 Immunology Cancer research Carcinoma Squamous Cell Tumor necrosis factor alpha Female medicine.drug |
| Zdroj: | IndraStra Global. |
| ISSN: | 2381-3652 |
| Popis: | ObjectiveHuman papillomavirus oncoproteins E6 and E7 down modulate Toll-like receptor (TLR) 9 expression in infected keratinocytes. We explored the status of expression and function of TLR7, TLR8, and TLR9 in primary human Langerhans cells (LCs) isolated from cervical tumors.MethodologySingle-cell suspensions were made from fresh tissues of squamous cell carcinoma (International Federation of Gynecology and Obstetrics stage IB2); myeloid dendritic cells were purified using CD1c magnetic activated cell separation kits. Langerhans cells were further flow sorted into CD1a+CD207+cells. Acute monocytic leukemia cell line THP-1–derived LCs (moLCs) formed the controls. mRNA from flow-sorted LCs was reverse transcribed to cDNA and TLR7, TLR8, and TLR9 amplified. Monocyte-derived Langerhans cells and cervical tumor LCs were stimulated with TLR7, TLR8, and TLR9 ligands. Culture supernatants were assayed for interleukin (IL) 1β, IL-6, IL-10, IL-12p70, interferon (IFN) α, interferon γ, and tumor necrosis factor (TNF) α by Luminex multiplex bead array. Human papillomavirus was genotyped.ResultsWe have for the first time demonstrated that the acute monocytic leukemia cell line THP-1 can be differentiated into LCs in vitro. Although these moLCs expressed all the 3 TLRs, tumor LCs expressed TLR7 and TLR8, but uniformly lacked TLR9. Also, moLCs secreted IL-6, IL-1β, and tumor necrosis factor α to TLR8 ligand and interferon α in response to TLR9 ligand; in contrast, tumor LCs did not express any cytokine to any of the 3 TLR ligands. Human papillomavirus type 16 was one of the common human papillomavirus types in all cases.ConclusionsCervical tumor LCs lacked TLR9 expression and were functionally anergic to all the 3: TLR7, TLR8, and TLR9 ligands, which may play a crucial role in immune tolerance. The exact location of block(s) in TLR7 and TLR8 signaling needs to be investigated, which would have important immunotherapeutic implications. |
| Databáze: | OpenAIRE |
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