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

Hindawi Publishing Corporation Mediators of Inflammation Volume 2014, Article ID 432785, 16 pages http://dx.doi.org/10.1155/2014/432785 Review Article Collaborative Action of Toll-Like and Nod-Like Receptors as Modulators of the Inflammatory Response to Pathogenic Bacteria Javier Oviedo-Boyso, Alejandro Bravo-Patiño, and Víctor M. Baizabal-Aguirre Molecular Immunology and Signal Transduction Laboratory, Centro Multidisciplinario de Estudios en Biotecnologı́a, Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo, Km. 9.5 s/n Carretera Morelia-Zinapécuaro, La Palma, Tarı́mbaro, C.P. 58893 Morelia, MICH, Mexico Correspondence should be addressed to Javier Oviedo-Boyso; and Vı́ctor M. Baizabal-Aguirre; Received 14 April 2014; Revised 11 June 2014; Accepted 27 June 2014; Published 1 December 2014 Academic Editor: Marisa I. Gómez Copyright © 2014 Javier Oviedo-Boyso et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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. 1. Introduction All living organisms are constantly challenged by microorganisms and a variety of particles (from air pollution and cellular stresses) that represent a health threat. To counteract this burden, the innate immune system needs to react promptly and adequately to eliminate them, while at the same time to preserve tissue normal function. In the last decade there has been an enormous progress in the study of the molecular mechanisms that allow the host to fight against any antigenic stimuli and to keep internal homeostasis. In general, the innate immune host defense includes three essential sequentially events: (1) microbial recognition, (2) activation of signaling pathways, and (3) effector mechanisms. Hosts are able to recognize distinct PAMPs present in microorganisms through a wide variety of PRRs. To date, a broad range of PRRs have been reported that include TLRs, NLRs, RLRs, and CLRs (for a complete description, see [1]). The different subcellular localization of PRRs and the broad array of PAMPs that can be recognized by them, allows the host to sense a large number of pathogen bacteria and develop an adequate immune response. Upon recognition of PAMPs by PRRs signal transduction pathways are activated that converge on transcription factors, such as NF-𝜅B, AP1 or IRFs. Activation of these transcription factors regulates the inflammatory and innate immune response through the expression of proinflammatory mediators and antimicrobial effectors. Since some pathogenic bacteria possess PAMPs that can be simultaneously recognized by several PRRs and this leads to the activation of common transcription factors, it is likely that a collaborative response among different signaling molecules may exert regulatory functions after recognition of 2 Mediators of Inflammation Table 1: Expression and localization of TLRs and NLRs in cellular types. Receptor Cellular type Localization Reference TLR1 TLR2 TLR3 Monocytes, mature macrophages, mast cell, and dendritic cells Monocytes, mature macrophages, and mast cell Dendritic cells Predominately in monocytes, mature macrophages, dendritic cells, mast cells, and intestinal epithelial cells Predominately in intestinal epithelial cells, monocytes, macrophages, and dendritic cells Monocytes, mature macrophages, and mast cell Monocytes, macrophages, and plasmacytoid dendritic cells Monocytes, macrophages, and mast cells Monocytes, macrophages, and plasmacytoid dendritic cells Macrophages, trophoblasts, and intestinal epithelial cells in response to L. monocytogenes Cell surface Cell surface Endosomes [191] [191] [191] Cell surface [191] Cell surface [191] Cell surface Endosomes Endosomes Endosomes Cell surface, but can colocalize with TLR2 in phagosome Cell surface and endoplasmic reticulum Colocalizes with TLR11 in endoplasmic reticulum [191] [191] [191] [191] [23–25] Intracellularly [50–52] Intracellularly [50–52] Intracellularly Intracellularly Intracellularly [109, 111, 114] [95, 96] [82] TLR4 TLR5 TLR6 TLR7 TLR8 TLR9 TLR10 TLR11 Macrophages, dendritic cells, and human embryonic kidney cells TLR12 Macrophages and dendritic cells NOD1 Macrophages, human mononuclear cells, intestinal epithelial cells, and dendritic cells Macrophages, neutrophils, dendritic cells, Paneth cells, human airway smooth muscle cells, and epithelial and endothelial cells Macrophages and gut epithelial cells Lymphocytes, respiratory epithelial cells, and myeloid cells Myeloid cells and human bronchial epithelial cells NOD2 NLRC4 NLRP1 NLRP3 pathogenic bacteria. Therefore, the aim of this review is to discuss recent findings on the collaborative activity of TLRs and NLRs in the modulation of the inflammatory response induced by virulence factors of pathogenic bacteria. 2. Recognition of Pathogenic Bacteria by the Host Animals, including humans, respond to a wide range of antigenic stimuli in order to preserve their homeostatic conditions [2]. Professional (macrophages, neutrophils, and dendritic cells) and nonprofessional (epithelial and endothelial cells) phagocytes express various PRRs that recognize PAMPs as well as other nonbiological stimuli [3, 4]. Among the most important PAMPs are lipoteichoic acid (LTA) and peptidoglycan (PGN) from Gram-positive bacteria, lipopolysaccharide (LPS) from Gram-negative bacteria, lipoarabinomannan (LAM) (...truncated)