J Bacteriol Virol.  2014 Sep;44(3):215-225. 10.4167/jbv.2014.44.3.215.

Toll-like Receptors and NOD-like Receptors in Innate Immune Defense during Pathogenic Infection

• Jin HS
• Park JK
• Jo EK

• KMID: 1726971
• DOI: http://doi.org/10.4167/jbv.2014.44.3.215

Abstract

In response to invading pathogens, the body immune system develops an immediate defense mechanism, i.e., innate immune response, which is detected in almost all living organisms including mammals, plants, insects, etc. Recent studies have identified numerous innate immune receptors that are able to recognize pathogen-associated molecular patterns and transduce the essential intracellular signaling cascades to mount early and successful host defenses against infectious challenge. Among innate immune receptors, we will focus on two important receptors, toll-like receptors (TLRs) and nucleotide binding oligomerization domain (Nod)-like receptors, and their major intracellular signaling pathways that culminate to activate innate immune effectors and inflammatory mediators during pathogen infection. In this review, we address the recent advances of understanding intracellular signaling mechanisms by which TLRs and NLRs activate host immune defense and inflammation. The role and regulatory mechanisms by which a subet of NLRs-associated inflammasome activation induce interleukin-1beta secretion and their relevance with host defense will be also discussed. Both TLR- and NLR-mediated intracellular signaling networks serve crucial roles in mounting resistance to bacterial and viral infection through synthesis of immune mediators and antimicrobial chemicals during infection.

Keyword

Toll-like receptors; Nod-like receptors; Inflammasome; Host defense; Infection; Innate immunity

MeSH Terms

Immune System
Immunity, Innate
Inflammation
Insects
Interleukin-1beta
Mammals
Toll-Like Receptors*
Interleukin-1beta
Toll-Like Receptors

Figure

• 

  Figure 1. Schematic diagrams of innate immune receptors. (Left) Toll-like receptor (TLR) signaling is activated by TLR ligands. TLRs which located in plasma membrane (TLR1, 2, 4, 5, 6, 11) activate NF-κB and MAPK (JNK, ERK, p38) signaling pathway via MyD88. Nucleic acid recognition by endosomal TLRs (TLR3, 7, 8, 9) induces production of type I interferon and proinflammatory cytokines via TRIF-IRF3 and MyD88-NF-κB signaling pathways, respectively. (Middle) NOD1 and NOD2 recognize γ-D-glutamyl-meso-diaminopimelic acid (meso-DAP) and muramic dipeptide (MDP) from bacterial cell wall components, respectively. NOD-induced proinflammatory responses require MAPK and NF-κB activation through the recruitment of adaptor molecule CARD9 and RICK. (Right) Certain members of NOD-like receptors (NLRs) participate in the activation of inflammasome complex consisting of NLRs, procaspase-1 and ASC in the cytosol. Multiple ligands or stimulators including various pathogen-associated molecular patterns, damage-associated molecular patterns, and microbes, have been identified to activate inflammasome complex to produce mature IL-1β and IL-18 through activation of caspase-1.

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