Chronic Lymphocytic Leukemia: A Paradigm of Innate Immune Cross-Tolerance
| Autor: | Elena Ruiz-Sainz, Rebeca Pérez de Diego, María Siliceo, Eduardo López-Collazo, Teresa Jurado-Camino, Laura Esteban-Burgos, Victor Toledano, Cristobal Belda, Carolina Cubillos-Zapata, Jose Angel Hernandez-Rivas, Enrique Hernández-Jiménez, Teresa Cobo, Raul Cordoba |
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| Rok vydání: | 2015 |
| Předmět: |
Male
T-Lymphocytes medicine.medical_treatment Chronic lymphocytic leukemia Immunology Down-Regulation Monocytes Immune tolerance Hypogammaglobulinemia Pathogenesis Immunity hemic and lymphatic diseases Immune Tolerance Humans Immunology and Allergy Medicine Aged Aged 80 and over TNF Receptor-Associated Factor 6 Innate immune system Gene Expression Regulation Leukemic business.industry Middle Aged medicine.disease Leukemia Lymphocytic Chronic B-Cell Immunity Innate Endotoxins MicroRNAs Leukemia Interleukin-1 Receptor-Associated Kinases Cytokine Cytokines Female business |
| Zdroj: | The Journal of Immunology. 194:719-727 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1402272 |
| Popis: | Infections are a significant cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). The pathogenesis of infections is multifactorial and includes hypogammaglobulinemia, conventional therapy with alkylating drugs, and recently, purine analogs and mAb-associated T cells. Patients without these risk factors also suffer from infections, although the mechanism remains unknown. In a cohort of 70 patients with CLL, we demonstrated that their monocytes were locked into a refractory state and were unable to mount a classic inflammatory response to pathogens. In addition, they exhibited the primary features of endotoxin tolerance, including low cytokine production, high phagocytic activity, and impaired Ag presentation. The involvement of miR-146a in this phenomenon was suspected. We found miR-146a target genes, such as IRAK1 and TRAF6, were manifestly downregulated. Our study provides a new explanation for infections in patients with CLL and describes a cross-tolerance between endotoxins and tumors. |
| Databáze: | OpenAIRE |
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