Abstract
Primary immunodeficiencies (PIDs) are severe defects in the capacity of the host to mount a proper immune response, and are characterized by an increased susceptibility to infections. Although classical immunodeficiencies have been characterized based on broad defects in cell populations (e.g. T/B cells or polymorphonuclear leukocytes) or humoral factors (e.g. antibodies or complement), specific immune defects based on well-defined molecular targets have been described more recently. Among these, genetic defects in pattern recognition receptors (PRRs), leading to impaired recognition of invading pathogens by the innate immune system, play an important role in specific defects against human pathogens. Defects have been described in three of the major families of PRRs: the Toll-like receptors, the C-type lectin receptors and the nucleotide-binding domain leucine-rich repeat-containing receptors. By contrast, no defects in the intracellular viral receptors of the RigI helicase family have been described to date. Defects in the PRRs show a broad variation in severity, have a narrow specificity for certain classes of pathogens, and often decrease in severity with age; these characteristics distinguish them from other forms of PIDs. Their discovery has led to important insights into the pathophysiology of infections, and may offer potential novel therapeutic targets for immunotherapy.
