title: Pattern recognitions receptors in immunodeficiency disorders.
abstract: Pattern recognition receptors (PRRs) recognize common microbial or host-derived macromolecules and have important roles in early activation and response of the immune system. Initiation of the innate immune response starts with the recognition of microbial structures called pathogen associated molecular patterns (PAMPs). Recognition of PAMPs is performed by germline-encoded receptors expressed mainly on immune cells termed pattern recognition receptors (PRRs). Several classes of pattern recognition receptors (PRRs) are involved in the pathogenesis of diseases, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), and Nod-like receptors (NLRs). Patients with primary immune deficiencies (PIDs) affecting TLR signaling can elucidate the importance of these proteins in the human immune system. Defects in interleukin-1 receptor-associated kinase-4 and myeloid differentiation factor 88 (MyD88) lead to susceptibility to infections with bacteria, while mutations in nuclear factor-κB essential modulator (NEMO) and other downstream mediators generally induce broader susceptibility to bacteria, viruses, and fungi. In contrast, TLR3 signaling defects are associated with susceptibility to herpes simplex virus type 1 encephalitis. Other PIDs induce functional alterations of TLR signaling pathways, such as common variable immunodeficiency in which plasmacytoid dendritic cell defects enhance defective responses of B cells to shared TLR agonists. Altered TLR responses to TLR2 and 4 agonists are seen in chronic granulomatous disease (CGD) and X-linked agammaglobulinemia (XLA). Enhanced TLR responses, meanwhile, are seen for TLRs 5 and 9 in CGD, TLRs 4, 7/8, and 9 in XLA, TLRs 2 and 4 in hyper IgE syndrome (HIES), and for most TLRs in adenosine deaminase deficiency. In this review we provide the reader with an update on the role of TLRs and downstream signaling pathways in PID disorders.
authors.affiliation: Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Esameil
authors.initials: E
authors.lastname: Mortaz
authors.affiliation: Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Adcock
authors.affiliation: Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Payam
authors.initials: P
authors.lastname: Tabarsi
authors.affiliation: Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti, University of Medical Sciences,Tehran, Iran.
authors.forename: Ilad Alavi
authors.initials: IA
authors.lastname: Darazam
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA), USA.
authors.forename: Masoud
authors.initials: M
authors.lastname: Movassaghi
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Sciences, Utrecht University, Utrecht, The Netherlands; Department of Immunology, Nutricia Research, Utrecht, the Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.affiliation: Chronic Respiratory Diseases Research Center and National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: hamidjamaati@hotmail.com.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Jamaati
authors.affiliation: Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Aliakbar
authors.initials: A
authors.lastname: Velayati
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism; D006801:Humans; D007154:Immune System Diseases / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000378:metabolism*
chemical_list: D051192:Receptors, Pattern Recognition
keywords: Chronic granulomatous disease; IgE syndrome; Primary immune deficiencies; TLRs