Abstract

New and exciting insights into the importance of the innate immune system are revolutionizing our understanding of immune defense against infections, pathogenesis, and the treatment and prevention of infectious diseases. The innate immune system uses multiple families of germline-encoded pattern recognition receptors (PRRs) to detect infection and trigger a variety of antimicrobial defense mechanisms. PRRs are evolutionarily highly conserved and serve to detect infection by recognizing pathogen-associated molecular patterns that are unique to microorganisms and essential for their survival. Toll-like receptors (TLRs) are transmembrane signalling receptors that activate gene expression programs that result in the production of proinflammatory cytokines and chemokines, type I interferons and antimicrobial factors. Furthermore, TLR activation facilitates and guides activation of adaptive immune responses through the activation of dendritic cells. TLRs are localized on the cell surface and in endosomal/lysosomal compartments, where they detect bacterial and viral infections. In contrast, nucleotide-binding oligomerization domain proteins and RNA helicases are located in the cell cytoplasm, where they serve as intracellular PRRs to detect cytoplasmic infections, particularly viruses. Due to their ability to enhance innate immune responses, novel strategies to use ligands, synthetic agonists or antagonists of PRRs (also known as 'innate immunologicals') can be used as stand-alone agents to provide immediate protection or treatment against bacterial, viral or parasitic infections. Furthermore, the newly appreciated importance of innate immunity in initiating and shaping adaptive immune responses is contributing to our understanding of vaccine adjuvants and promises to lead to improved next-generation vaccines.

Highlights

  • Kenneth L Rosenthal PhDCYTOPLASMIC PATHOGEN RECOGNITION RECEPTORS Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) at the cell surface or in endosomal/lysosomal membranes, a number of pathogens invade the cytosol

  • De nouveaux aperçus passionnants de l’importance du système immunitaire inné révolutionnent notre compréhension de la défense immunologique contre les infections, de la pathogenèse, du traitement et de la prévention des maladies infectieuses

  • The genital tract has been considered to be a poor immune inductive site, especially following immunization with nonreplicating antigens, Kwant and Rosenthal [89] showed that IVAG immunization of female mice with recombinant subunit herpes simplex virus (HSV)-2 gB plus CpG induced higher levels of gB-specific IgG and IgA antibodies in serum and vaginal washes versus mice immunized with antigen alone, and that mice immunized with gB plus CpG were better protected against vaginal infection with HSV-2

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Summary

Kenneth L Rosenthal PhD

CYTOPLASMIC PATHOGEN RECOGNITION RECEPTORS TLRs recognize PAMPs at the cell surface or in endosomal/lysosomal membranes, a number of pathogens invade the cytosol These pathogens are detected by cytoplasmic PRRs. Recently, two families of these cytoplasmic receptors have been cloned, including the nucleotide-binding oligomerization domain (NOD)-LRR proteins [38,39] and caspase-activation recruitment domain (CARD)-helicase proteins [40]. The mechanisms by which PRRs mediate host defense against pathogens are the focus of intense research Due to their ability to enhance innate immune responses, novel strategies to use ligands, synthetic agonists or antagonists of PRRs ( known as ‘innate immunologicals’) can be used as stand-alone agents to provide protection or treatment against infection with intracellular bacteria, parasites and viruses. Studies of pregnant mice show that CpG ODN treatment significantly increased resistance to infection by bacteria and reduced transplacental transmission of pathogen from mother to fetus [72]

INNATE IMMUNOLOGICALS AS MUCOSAL MICROBICIDES
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