Synergism between TLRs and NOD1/2 in Oral Epithelial Cells

2008 ◽  
Vol 87 (7) ◽  
pp. 682-686 ◽  
Author(s):  
A. Uehara ◽  
H. Takada
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Oral Bacteria ◽  
Innate Immune ◽  
Oral Epithelium ◽  
Innate Immune Responses ◽  
Oral Epithelial Cells ◽  
Oral Epithelial ◽  
Pro Inflammatory Cytokines

Oral epithelium is the first barrier against oral bacteria in periodontal tissue. Oral epithelial cells constitutively express Toll-like receptors (TLRs) and NOD1/2, functional receptors which induce the production of antibacterial factors such as peptidoglycan recognition proteins (PGRPs) and β-defensin 2, but not pro-inflammatory cytokines such as interleukin (IL)-8. In this study, we hypothesized that innate immune responses in the oral epithelium are enhanced in inflamed tissue. We found that NOD1 and NOD2 agonists, in combination with TLR agonists, synergistically induced production of PGRPs and of β-defensin 2 in human oral epithelial cells via NF-κB. In contrast, co-stimulation with NOD1/2 and TLR ligands had no effect on the production of pro-inflammatory cytokines (IL-6, IL-8, and monocyte chemoattractant protein-1). These findings indicate that, in innate immune responses to invading microbes, a combination of signaling through TLRs and NODs leads to the synergistic activation of antibacterial responses in the oral epithelium.

Toll-like Receptors, NOD1, and NOD2 in Oral Epithelial Cells

2006 ◽  
Vol 85 (6) ◽  
pp. 524-529 ◽  
Author(s):  
Y. Sugawara ◽  
A. Uehara ◽  
Y. Fujimoto ◽  
S. Kusumoto ◽  
K. Fukase ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Host Defense ◽  
Inflammatory Responses ◽  
Immunohistochemical Analysis ◽  
Oral Bacteria ◽  
Innate Immune ◽  
Oral Epithelium ◽  
Toll Like Receptor ◽  
Oral Epithelial Cells ◽  
Oral Epithelial

Oral epithelium might be the first barrier against oral bacteria in periodontal tissue. We hypothesized that oral epithelium is endowed with innate immune receptors for bacterial components, which play roles in host defense against bacterial infection without being accompanied by excessive inflammatory responses. We found clear expression of Toll-like receptor (TLR)4 as well as TLR2, and strong expression of NOD1 and NOD2 in normal oral epithelial tissues by immunohistochemical analysis. We also showed that primary oral epithelial cells in culture expressed these molecules using PCR, flow cytometry, and immunostaining. In inflamed oral epithelium, cell-surface localizations of TLR2 and TLR4 were more clearly observed than in healthy tissue. Upon stimulation with synthetic ligands for these receptors, the expression of β-defensin 2 was markedly up-regulated. These findings indicate that these molecules in oral epithelial cells are functional receptors that induce antibacterial responses.

scholarly journals Regulation of the Peptidoglycan Amidase PGLYRP2 in Epithelial Cells by Interleukin-36γ

2018 ◽  
Vol 86 (9) ◽  
Author(s):  
Glen M. Scholz ◽  
Jacqueline E. Heath ◽  
Jiamin Aw ◽  
Eric C. Reynolds
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Bacterial Pathogen ◽  
Oral Bacteria ◽  
Oral Epithelium ◽  
Content Type ◽  
Oral Epithelial Cells ◽  
Mitogen Activated Protein ◽  
Mucosal Homeostasis ◽  
Oral Epithelial

ABSTRACT Interleukin-36 (IL-36) cytokines are important regulators of mucosal homeostasis and inflammation. We have previously established that oral epithelial cells upregulate IL-36γ expression in response to the bacterial pathogen Porphyromonas gingivalis. Here, we have established that IL-36γ can stimulate the gene expression of mechanistically distinct antimicrobial proteins, including the peptidoglycan amidase PGLYRP2, in oral epithelial cells (e.g., TIGK cells). PGLYRP2 gene expression was not stimulated by either IL-17 or IL-22, thus demonstrating selectivity in the regulation of PGLYRP2 by IL-36γ. The IL-36γ-inducible expression of PGLYRP2 was shown to be mediated by IRAK1- and p38 mitogen-activated protein (MAP) kinase-dependent signaling. Furthermore, our finding that IL-36γ-inducible PGLYRP2 expression was reduced in proliferating TIGK cells but increased in terminally differentiating cells suggests that control of PGLYRP2 expression is associated with the maturation of the oral epithelium. PGLYRP2 expression in TIGK cells can also be directly stimulated by oral bacteria. However, the extracellular gingipain proteases (Kgp and RgpA/B) produced by P. gingivalis, which are critical virulence factors, can antagonize PGLYRP2 expression. Thus, the expression of IL-36γ by oral epithelial cells in response to P. gingivalis might enable the subsequent autocrine stimulation of PGLYRP2 expression. In summary, our data identify how IL-36γ may promote oral mucosal homeostasis by regulating PGLYRP2 expression.

scholarly journals NOD1 and NOD2 Mediate Sensing of Periodontal Pathogens

2009 ◽  
Vol 89 (2) ◽  
pp. 186-191 ◽  
Author(s):  
T. Okugawa ◽  
T. Kaneko ◽  
A. Yoshimura ◽  
N. Silverman ◽  
Y. Hara
Keyword(s):  
Immune Responses ◽  
Fusobacterium Nucleatum ◽  
Innate Immune ◽  
Periodontal Pocket ◽  
Innate Immune Responses ◽  
Periodontal Pathogens ◽  
Human Embryonic Kidney Cells ◽  
Oral Epithelial Cells ◽  
Oral Epithelial ◽  
Oligomerization Domain

In bacterial infection, Nucleotide-binding Oligomerization Domain (NOD) 1 and NOD2 induce innate immune responses by recognizing fragments of the bacterial component peptidoglycan (PGN). To determine the roles of these receptors in detection of periodontal pathogens, we stimulated human embryonic kidney cells expressing NOD1 or NOD2 with heat-killed Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum or their soluble PGNs (sPGNs). All bacteria and their sPGNs could stimulate activation of NF-κB. However, there were differences in NOD1- and NOD2-stimulatory activities among the species of bacteria. P. gingivalis showed weaker NOD1- and NOD2-stimulatory activities than did other bacteria. These differences in activities were confirmed by production of interleukin-8 from oral epithelial cells stimulated with sPGNs. These findings indicate that both NOD1 and NOD2 might be involved in the recognition of periodontal pathogens, and that the weak NOD-stimulatory property of P. gingivalis might be helpful for survival in the periodontal pocket.

scholarly journals The effective regulation of pro- and anti-inflammatory cytokines induced by combination of PA-MSHA and BPIFB1 in initiation of innate immune responses

Open Medicine ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 299-307 ◽  
Author(s):  
Weiqiang Zhou ◽  
Zhiwen Duan ◽  
Biao Yang ◽  
Chunling Xiao
Keyword(s):  
Inflammatory Response ◽  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Late Phase ◽  
Upper Airway ◽  
Innate Immune ◽  
Antibody Array ◽  
Innate Immune Responses ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractPA-MSHA and BPIFB1 play especially important roles in triggering innate immune responses by inducing production of pro- or anti-inflammatory cytokines in the oral cavity and upper airway. We found that PA-MSHA had a strong ability to activate pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. However, BPIFB1 alone did not express a directly inductive effect. With incubation of PA-MSHA and BPIFB1, the combination can activate the CD14/TLR4/MyD88 complex and induce secretion of subsequent downstream cytokines. We used a proteome profiler antibody array to evaluate the phosphokinases status with PA-MSHA and BPIFB1 treatment. The results showed that the activation of MAPK, STAT, and PI-3K pathways is involved in PA-MSHA-BPIFB1 treatment, and that the related pathways control the secretion of targeting cytokines in the downstream. When we assessed the content changes of cytokines, we found that PA-MSHA-BPIFB1 treatment increased the production of pro-inflammatory cytokines in the early phase of treatment and induced the increase of IL-4 in the late phase. Our observations suggest that PA-MSHA-BPIFB1 stimulates the release of pro-inflammatory cytokines, and thereby initiates the innate immune system against inflammation. Meanwhile, the gradual release of anti-inflammatory cytokine IL-4 by PA-MSHA-BPIFB1 can also regulate the degree of inflammatory response; thus the host can effectively resist the environmental risks, but also manipulate inflammatory response in an appropriate and adjustable manner.

scholarly journals Herpes Simplex Virus 1 Infection of Neuronal and Non-Neuronal Cells Elicits Specific Innate Immune Responses and Immune Evasion Mechanisms

2021 ◽  
Vol 12 ◽  
Author(s):  
Amanda L. Verzosa ◽  
Lea A. McGeever ◽  
Shun-Je Bhark ◽  
Tracie Delgado ◽  
Nicole Salazar ◽  
...  
Keyword(s):  
Herpes Simplex ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Host Cell ◽  
Signaling Pathways ◽  
Sensory Neurons ◽  
Immune Evasion ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Hsv 1

Alphaherpesviruses (α-HV) are a large family of double-stranded DNA viruses which cause many human and animal diseases. There are three human α-HVs: Herpes Simplex Viruses (HSV-1 and HSV-2) and Varicella Zoster Virus (VZV). All α-HV have evolved multiple strategies to suppress or exploit host cell innate immune signaling pathways to aid in their infections. All α-HVs initially infect epithelial cells (primary site of infection), and later spread to infect innervating sensory neurons. As with all herpesviruses, α-HVs have both a lytic (productive) and latent (dormant) stage of infection. During the lytic stage, the virus rapidly replicates in epithelial cells before it is cleared by the immune system. In contrast, latent infection in host neurons is a life-long infection. Upon infection of mucosal epithelial cells, herpesviruses immediately employ a variety of cellular mechanisms to evade host detection during active replication. Next, infectious viral progeny bud from infected cells and fuse to neuronal axonal terminals. Here, the nucleocapsid is transported via sensory neuron axons to the ganglion cell body, where latency is established until viral reactivation. This review will primarily focus on how HSV-1 induces various innate immune responses, including host cell recognition of viral constituents by pattern-recognition receptors (PRRs), induction of IFN-mediated immune responses involving toll-like receptor (TLR) signaling pathways, and cyclic GMP‐AMP synthase stimulator of interferon genes (cGAS-STING). This review focuses on these pathways along with other mechanisms including autophagy and the complement system. We will summarize and discuss recent evidence which has revealed how HSV-1 is able to manipulate and evade host antiviral innate immune responses both in neuronal (sensory neurons of the trigeminal ganglia) and non-neuronal (epithelial) cells. Understanding the innate immune response mechanisms triggered by HSV-1 infection, and the mechanisms of innate immune evasion, will impact the development of future therapeutic treatments.

Sign in / Sign up

Export Citation Format

Share Document