Defects in innate immunity: Receptors and signaling components

Abstract

The innate immunity is the first line of defense against pathogens, exerting fast and effectiveresponses via preformed receptors. Toll-like receptors (TLRs) recognize specific molecular patterns found in a broad rangeof microbial pathogens such as bacteria and viruses, triggering inflammatory and antiviral responses, which result in the eradication of invading pathogens. Primary immunodeficiency diseases with primary defects in TLR signaling include Interleukin-1 receptor-associated kinase-4 (IRAK-4) deficiency, UNC-93B deficiency and TLR3 deficiency. These defects predispose patients to a narrow range of infections; pneumococcal infections in IRAK-4 deficiency, and herpes simplex encephalitis in UNC-93B and TLR3 deficiencies. Anhidrotic ectodermal dysplasia with immunodeficiency is caused by defects in the nuclear factor NF-κB signaling. In these disorders, TLR signaling is also impaired. Poor inflammatory response despite severe infection and absence of fever are characteristic of TLR defects. Mendelian susceptibility to mycobacterial diseases are characterized by recurrent and severe infections caused by weakly virulent organisms, such as environmental mycobacteria and Bacille Calmette-Guérin, and is associated with impaired IL-12/Interferon-γ dependent innate immunity. WHIM (warts, hypogammaglobulinemia, infections, myelokathexis) syndrome is a primary immunodeficiency disease caused by mutation of the CXCR4 chemokine receptor gene. Both innate and adaptive immunity are impaired in this disorder. Epidermodysplasia verruciformis is a rare autosomal recessive disorder associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses (HPVs). © 2008 Springer Berlin Heidelberg.