Collaborative Action of Toll-Like and Nod-Like Receptors as Modulators of the Inflammatory Response to Pathogenic Bacteria

Abstract

Early sensing of pathogenic bacteria by the host immune system is important to develop effective mechanisms to kill the invader. Microbial recognition, activation of signaling pathways, and effector mechanisms are sequential events that must be highly controlled to successfully eliminate the pathogen. Host recognizes pathogens through pattern-recognition receptors (PRRs) that sense pathogen-associated molecular patterns (PAMPs). Some of these PRRs include Toll-like receptors (TLRs), nucleotide-binding oligomerization domain-like receptors (NLRs), retinoic acid-inducible gene-I- (RIG-I-) like receptors (RLRs), and C-type lectin receptors (CLRs). TLRs and NLRs are PRRs that play a key role in recognition of extracellular and intracellular bacteria and control the inflammatory response. The activation of TLRs and NLRs by their respective ligands activates downstream signaling pathways that converge on activation of transcription factors, such as nuclear factor-kappaB (NF-κB), activator protein-1 (AP-1) or interferon regulatory factors (IRFs), leading to expression of inflammatory cytokines and antimicrobial molecules. The goal of this review is to discuss how the TLRs and NRLs signaling pathways collaborate in a cooperative or synergistic manner to counteract the infectious agents. A deep knowledge of the biochemical events initiated by each of these receptors will undoubtedly have a high impact in the design of more effective strategies to control inflammation.

Secretory IgA Deficiency in Individual Small Airways Is Associated with Persistent Inflammation and Remodeling

“…Bacteria can initiate innate immune signaling in the epithelium through activation of Toll-like receptors, leading to activation of the NF-kB pathway (21)(22)(23). To investigate whether airway surface SIgA deficiency and the presence of bacteria within the epithelial layer correlate with NF-kB activation, we performed fluorescent immunostaining for an activated form of the RelA(p65) component of NF-kB (phosphoserine 276 [24][25][26]) on serial sections ( Figure 5A).…”

Activation of p38 and Erk Mitogen-Activated Protein Kinases Signaling in Ocular Rosacea

“…14,22 These receptors are well known to promote p38 and Erk activation, 23,24 and these pathways have been shown to mediate multiple keratinocyte responses. For example, TLR2-mediated p38 and Erk activation was required for the inflammatory and antimicrobial responses of keratinocytes challenged with streptococcal M1 protein, 25 Staphylococcus epidermidis LP01 lipopeptide, 26 or Candida albicans phospholipomannan.…”

Subversion of Cell-Autonomous Host Defense by Chlamydia Infection

“…Secreted effector proteins as well as components of their secretion machinery are recognized by intracellular NLRs and thereby induce assembly of a multiprotein complex called inflammasome (Lamkanfi and Dixit 2011). Dependent on the N-terminal domain of NLRs, which is important for the interaction with the adaptor protein ASC, they are categorized into NLRPs containing a PYR domain or NLRCs with a CARD domain (Oviedo-Boyso et al 2014;Schroder and Tschopp 2010). Upon ligand binding or sensing of intracellular stress signals-so-called danger-associated molecular patterns (DAMPs)-NLRs associate with the adaptor protein ASC and induce autocatalytic cleavage of pro-Caspase-1 to form an active inflammasome (Lamkanfi et al 2007).…”