Toll‐like receptors: key activators of leucocytes and regulator of haematopoiesis

• Published in: British journal of haematology 2007-10, Vol.139 (2), p.185-193
• Main Authors: McGettrick, Anne F., O'Neill, Luke A. J.
• Format: Article
• Language: English
• Subjects: Apoptosis; Biological and medical sciences; B‐cell and T‐cell proliferation; chronic lymphocytic leukaemia; haematopoiesis; Hematologic and hematopoietic diseases; Hematopoiesis - physiology; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Activation; Lymphocytes - physiology; Medical sciences; neutrophil apoptosis; Neutrophils - physiology; Toll-Like Receptors - agonists; Toll-Like Receptors - metabolism; Toll‐like receptors
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2007.06802.x

Toll‐like receptors (TLRs) play a critical role in the induction of the immune response to invading pathogens. The detection of pathogens by TLRs initiates a signalling cascade that results in the activation of transcription factors such as nuclear factor (NF)‐κB and interferon regulatory factors leading to the production of pro‐inflammatory cytokines and type 1 interferons. Five cytoplasmic adaptors, MyD88, Mal, Trif, TRAM and SARM, are utilized by the TLRs to activate these signalling pathways. Through the years the main focus of research has been on the activation and function of TLRs in monocytic cells. This review discusses several additional roles of TLRs. TLR activation plays a role in influencing the differentiation of haematopoietic stem cells. Their activation also prevents apoptosis in neutrophils following pathogen invasion. B cells and T cells proliferation and differentiation is influenced by TLR activation and the possible therapeutic benefits of using TLR ligands for the treatment of chronic lymphocytic leukaemia will also be discussed.