dentistry

1. TOLL LIKE RECEPTORS
IMMUNOLOGY
Presented by
DR.R.DHIVYA.,MDS

2. CONTENTS
• Introduction
• Definition
• Origin and Discovery
• Structure of TLR
• Toll receptor superfamily
• Classification of TLR
• TLR Ligands
• Localization of TLR’s
• Regulation by TLR’s on APC
• TLR signalling ellicts inflammation
• TLR Signalling mechanism
• Role of TLR in Innate and Adaptive immunity
• Role of TLR in Periodontics
• Double edge Sword
• Role of virus in TLRS
• Recent studies
• Conclusion
• Reference

3. INTRODUCTION
SPECIFIC
ADAPTIVE
INNATE
NON-
SPECIFIC
Primitive
bone marrow
cells
Advanced
Lymphatic
cells

4. PAMPs Pathogen Associated Molecular Patterns
PRRs Pattern Recognition Receptors

5. PAMPs Vs Virulence factors
PAMPs Virulence factors
Perform essential physiological functions
Detect the presence of infection
DID NOT evolve to interact with the host immune
system
A microbial adaptation to the unique environment
within the host.
Interact with the host
Invade host cells
Colony formation
Avoid host immune responses
Adjust to new nutrient sources.
Incapable of sustaining mutations
Conserved within a class of microbes
Multiple virulence factors that can vary between
different strains and species of pathogens.
Genes encoding PAMPs are expressed constitutively. Genes encoding virulence factors are turned on and
off depending on the stage of the infection cycle

6. DEFINITION
• A family of pattern-recognition receptors used as a tool to trigger an inflammatory response
to microbial invasion. They are single, membrane-spanning, non-catalytic receptors usually
expressed on sentinal cells such as macrophages and dentritic cells , that recognize structurally
conserved molecules derived from microbes. - Christiane Nüsslein-Volhard - 1995
• The ability of immune system to recognize molecules that are broadly shared by pathogens is, in
part, due to the presence of Immune receptors called toll-like receptors.
• Act as a bridge between Innate and Adaptive immunity by mediating dendritic cell maturation and
activation of pathogen-specific T lymphocytes.
• On interaction with PAMPs, TLRs transmit this information through intracellular signaling pathways,
resulting in activation of innate immune cells.

7. ORIGIN AND DISCOVERY
The gene in question, when mutated, makes the Drosophila (fruit fly) embryo look unusual.
The researchers were so surprised that they spontaneously shouted out in German "Das ist ja toll!"
which translates as "That's great!".
[The Nobel Prize in Physiology or Medicine 1995: Edward B. Lewis, Christiane
Nüsslein-Volhard, Eric F.Wieschaus]
Toll: Origin of the word (1985)

8. Important milestones in the discovery of Toll receptors

9. Structure of toll-like receptor(TLR)
TLRs are type I transmembrane proteins having:
• Ecto domain :amino terminal domain composed of repeated
motifs rich in leucine and known as lecine rich repeats(LRRs).
Leucine rich repeats has 1 to 2 cysteine residues.
• Transmembrane region
• Cytosolic domain: called as Toll/Interleukin I
receptor (TIR) domain.
TIR domain has 3 regions, highly conserved
among all family members, called boxes 1,2 in
and 3. These serve as binding site for intra
cellular proteins that participate in signalling
Pathway – Signalling box

10. • TLRs, together with the IL-1 receptors, form a receptor superfamily known as the “Interleukin-1
Receptor/TLR Superfamily”; all the members of this family have in common a so-called TIR-1 domain.
• Three subgroups of TIR domains exist.
• Proteins with subgroup 1 TIR domains are receptors for ILs that are produced by macrophages, monocytes and
dendritic cells, and all have extracellular immunoglobulin (Ig) domains.
• Proteins with subgroup 2 TIR domains are classical TLRs and bind directly or indirectly to molecules of microbial
origin.
• A third subgroup of proteins containing TIR domains consists of adaptor proteins that are exclusively cytosolic
and mediate signaling from proteins of subgroups 1 and 2.
The toll-like receptor superfamily

11. Types Of TLRs
• TLR can be classified as
- cell surface TLRs
- intracellular TLRs
• Cell surface TLRs seem to recognize microbial
products whereas intracellular TLRs recognize nucleic
acids.
• Include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR
7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13,
though the latter three are not found in humans.

12. RECEPTOR CELL TYPE REGULATION
TLR1 Ubiquitous No significant
regulation
TLR2 PMN,
Dentritic cells
& monocytes
Induced by LPS
Lipoarabinomanan
lipoteichoic acid
TLR3 Dentritic
cells&
Natural killer
cells
Recognises RNA
TLR4
Macrophages,
Dentritic cells
Proinflammatory
cytokines
and bacterial
products
TLR5 Monocytes,
Dentritic cells
epithelial
cells, T cells
Bacterial flagella
Types Of TLRs
12
TLR6 Bcells,Monocy
tes
Proinflammato
ry cytokines
TLR7 Bcells.
Dentritic cells
Synthetic
analogues
TLR8 Monocytes,
Tcells
gamma
interferon
,LPS
TLR9 Bcells,PMN,
Macrophages
and
Microglial cells
CpG MOTIF
of bacterial
DNA
TLR10 Bcells ,
Dentritic cells
NO significant
modulation

13. TLR LIGANDS
 Those TLRs (i.e. TLRs 1, 2, 4, 5 and 6) that recognize extracellular
microbial structures are expressed on the host cell surface.
 TLR2, in cooperation with its signaling partners, TLR1 or TLR6, detect
mostly microbial cell wall components, such as lipoproteins, lipoteichoic
acid (LTA), fimbriae, or yeast zymosan .
 TLR4 and TLR5 recognize lipopolysaccharide (LPS) and bacterial
flagellin, respectively, whereas no ligand has been identified for TLR10.
 Those TLRs (i.e. TLRs 3, 7, 8 and 9) specializing in detecting viral or
bacterial nucleic acids are expressed intracellularly on endocytic vesicles.
 TLR3 recognizes double-stranded viral RNA, TLR7 and TLR8 recognize
single-stranded viral RNA and TLR9 detects microbial CpG DNA.

14. • TLR 1  Triacyl Lipopeptides
• TLR 2  Lipoproteins, Peptidoglycan, Lipoteichoic acid, Zymosan, Porphyromonas
gingivalis lipopolysaccharide & fimbriae, Capnocytophaga ochracea
lipopolysaccharide
• TLR 3  Double stranded RNA, Polyinosine-polycytidylic acid
• TLR 4  Escherichia coli lipopolysaccharide, Porphyromonas gingivalis
lipopolysaccharide, Actinobacillus actinomycetemcomitans lipopolysaccharide,
Fusobacterium nucleatum lipopolysacchride
• TLR 5  Flagellin
• TLR 6 Peptidoglycan, Lipoteichoic acid, Diacyl lipopeptides, Zymosan
• TLR 7 Imidazquinoline
• TLR 8 Single stranded RNA, Imidazquinoline
• TLR 9 Bacterial DNA, CpG oligodeoxynucleotide
• TLR 10 Not determined

15. • TLRs are expressed on cell surface and within intracellular
vesicles( ER, endosomes, lysosomes etc.)
• TLRs on cell surface recognize components of microbial
membrane while those expressed within intracellular
vesicles recognize foreign nucleic acids.
• Protein PRAT4A regulates exit of TLR1,TLR2,TLR4,
TLR7 and TLR9 from ER to respective places.
• Gp96 – ER resident heat shock protein 90 family
acts as chaperone for most TLRs .
LOCALIZATION OF TLRS

16. Regulation of Th Cell development by TLR’s on APC
 Recognition of pathogens - TLRs - cytokines - IL-12 and IL-18 in APCs –
”Instructive cytokines “ – drive Naïve T cells – TH 1 cells.
 Pathogens - captured - phagocytosis, endocytosis or via TLRs themselves
 Captured pathogens - processed - presented to T cells – MHC antigen.
 For expansion of antigen-specific T cell clones - up-regulated expression
of costimulatory molecules on the cell surface of APCs.
 This up-regulation is also triggered by TLR signaling.TLR-stimulated APCs
mainly induce TH1 development.
 It remains unclear at present whether TLRs in APCs are involved in TH2
development

17. TLR signalling ellicts inflammation
 Pathogens - enter host - breached epithelial barrier, leads - activation of
macrophage - TLRs by pathogen-derived molecules, including LPS.
 TLR signaling - inflammatory cytokines, - near the site of infection to
recruit neutrophils and induce neutrophil production of antimicrobial
molecules, including peptides, reactive oxygen species (e.g. H2O2 and
superoxide anion), and leukotrienes.
 Cytokines also travel throughout the body and induce systemic effects.
 Both macrophages and neutrophils act to limit infection by phagocytosis
of pathogens.

18. TLR Signaling
- TLR signaling cascades are separated into two groups:
- The myeloid differentiation primary-response protein 88-dependent pathway
- The myeloid differentiation primary-response protein 88-independent pathway
- The myeloid differentiation primary-response protein 88-dependent pathway is essential for
most TLR-mediated cell activations.
- The molecules that are structurally related to myeloid differentiation primary-response protein
88 led to identification of other adaptor proteins which includes :

19. 5 cytoplasmic adaptor proteins have been identified for TLR signalling cascades (Beutler et al 2004)
 MyD88 (Myleoid differentiation factor 88)
 TRIF (Toll/interlukin-1R domain containing adaptor-inducing interferon β)
 TIRAP (or Mal) (MyD88 adaptor-like) (Toll interlukin-1 receptor containing adaptor protein)
 TRAM (TRIF-related adaptor molecule)
 SARM (sterile alpha and HEAT/ Armadilo motif protein)

20. TLR Signaling

21. TLR 4
MAL / MyD88 TRAM / TIRAF
MAPK
Interferon regulatory
factor -3
NF - kβ
Proinflammatory cytokines and
TYPE I Interferons
A fifth known adaptor, designated sterile alpha and HEAT / Armadilo motif protein-1,
functions as a negative regulator of TLR signalling.

22.  The MyD88 dependent pathway leads to subsequent activation of IRAK (IL-1R-associated kinase),
TRAF6, and ultimately NF-kB and it is essential for cytokine induction.
 MyD88-independent pathway does not activate IRAK and leads to activation of NF-kB with delayed
kinetics.
 This independent pathway requires different adaptor proteins, such as TIRAP, TRIF, and TRAM,
and probably does not lead to cytokine induction.
 Another interesting aspect of MyD88-independent signaling is that it can induce dendritic cell
maturation.
 Rather, it is related to interferon-β secretion and indirect upregulation of IFN-dependent genes.

24. Role of TLR in Innate and Adaptive immunity
 It is predominantly expressed on cells of the innate immune system, including neutrophils,
monocytes/macrophages, and dendritic cells.
 Neutrophils are the first innate immune cells to migrate to sites of infection and utilize TLRs to
recognize and respond to microbial challenge.
 Macrophages/monocytes, also the first line of defense, bind to microbial pathogens through TLRs.
 They play a key role in host defense by recognizing, engulfing and killing microorganisms.
 The binding of PAMPs to monocyte TLRs can influence the type of adaptive immune response

25. Development of adaptive immunity is controlled through activation of innate immune cells antigen
presenting dendritic cells.
TLRs of resident immature dendritic cells
detect the PAMPs
Transmit the information through signaling
pathways
Activation of dendritic cells
Production of cytokines and chemokines
critical for T-cell priming and differentiation
Two subpopulations of dendritic cell precursors have beenidentified in human blood: myeloid dendritic
cells and plasmacytoid dendritic cells expressing different TLRs
MDC – TLR – 1 - 6,8,10
PDC – TLR - 1,6,7,9 but not 2,5,8.

26. • TLRs are also expressed on the cells responsible for adaptive immunity, i.e. B and T lymphocytes
• T cells predominate in stable periodontal lesions . Proportion of B cells and plasma cells is increased in
progressive lesions
• The TLRs expressed on T lymphocytes and their respective ligands can directly modulate T cell function.
• These TLRs act as co-stimulatory receptors to enhance proliferation and/or cytokine production of T-cell
receptor-stimulated T lymphocytes.
• Different TLR ligands instruct dendritic cells to stimulate distinct T helper cell responses.
• E. coli lipopolysaccharide and flagellin, which trigger TLR 4 and TLR 5, respectively, cause human dendritic cells
to induce a Th1 response via IL-12 production.
• In contrast, the TLR 2 ligand and P. gingivalis lipopolysaccharide cause induction of a Th 2 response.

27. Role of TLRs in Periodontitis

28. Expression of TLR

29. Toll-like receptors expressed by immune cells
• Neutrophils  TLR 1, 2, 4-10
• Monocytes/macrophages  TLR 1, 2, 4-8
• Myeloid dendritic cells  TLR 1-6, 8, 10
• Plasmacytoid dendritic cells TLR 1, 6, 7, 9
• B lymphocytes  TLR 1, 3, 6, 7, 9, 10
• T lymphocytes (Th1/Th2)  TLR 2, 3, 5, 9
• T lymphocytes (regulatory)  TLR 2, 5, 8

30. GINGIVITIS
(STRONG INNATE IMMUNE RESPONSE)
Th 1
Cell mediated immunity
Protective Antibody Production
Stable lesion
PERIODONTITIS
(POOR INNATE IMMUNE RESPONSE)
PERIODONTOPATHIC BACTERIA
(polyclonal Bcell activation)
Th2
Non protective antibody production
Progressive lesion

31. Gingival Epithelial cells
• TLR 2, 3, 4, 5, 6, 9
• Increased attachment and migration of leucocytes towards antigen on lumen of the
pocket, also induces production of Interleukin-8 (IL-8) as well as Matrix
metalloproteinases.
Gingival fibroblasts
• TLR 2, 4, 9
• Increased production of Interleukin-8 as well as other pro-inflammatory
cytokines.

32. Endothelium
• TLR 1, 3, 4, 5
• Production of pro-inflammatory cytokines and chemokines, migration of immune cells
towards gingival sulcus.
Osteoclasts
• TLR 2, 4
• Enhanced survival of osteoblasts and increased osteoclastic activities.

33. Cementoblasts
• TLR 2, 4
• Down regulation of RANKL
Periodontal ligament fibroblasts
• TLR 2, 4
• Enhanced production of pro-inflammatory cytokines, release of proteases causing
direct destruction of surrounding tissues.

34. • TLR signaling results in innate immune responses involving the release of the antibacterial β-
defensins cathelicidin and calprotectin, neutrophil chemoattractant (interleukin-8)
• TLR signaling limits microbial invasion and prevents commensal organisms from breaching the
epithelial barrier, thereby maintaining gingival health.
• TLR2, 4, 7 and 9 is upregulated in periodontitis lesions (Kajita K et al Oral Microbiol
Immunol 2007)
• TLR2 is detectable in gingival epithelia in the spinous epithelial layer (Kusumoto Y et al J
Periodontol 2004)

35. • Gingival fibroblasts express TLR-2 and 4 and their levels of expression are elevated in
periodontitis. ( Wang PL et al Biochem Biophys Res Commun 2003)
• TLR activation influences osteoclastogenesis (Aoki M et al Biochem Biophys Res Commun
2006), (Kikuchi T et al J Immunol 2001).
• TLRs (like 2, 4 and 9) enhance the survival rates of mature osteoclasts.(Takami M et al j
Immunol 2002)

36. TLR – Double edged sword

37. • The periodontium is continually exposed to dental plaque, which harbors many commensal and
pathogenic oral microorganisms.
• Periodontal tissues express different types of TLRs, allowing them to actively participate in the
innate immune response against these oral microorganisms.
• Thus, these TLRs provide a first line of defense in maintaining periodontal health.
• It has been suggested recently that the oral mucosa develops tolerance after repeated exposure
to bacterial products.
POSITIVE EDGE

38. • Down-regulation of TLR expression and inhibition of intracellular signaling may be the
underlying mechanisms of tolerance.
• However, recent research has indicated that under steady-state conditions, activation of TLRs
by commensal bacteria is critical for the maintenance of oral health.
• Gingival epithelial cells express TLR 2, 3, 4, 5, 6 and 9 and recognize various microorganisms
with the help of these receptors.
• These TLRs expressed on the gingival epithelium continually interact with oral microorganisms
that form biofilms on tooth surfaces.

39. • This TLR signaling results in innate immune responses involving the release of the antibacterial
β-defensins , cathelicidin and calprotectin, as well as neutrophil chemoattractant (IL-8).
• Therefore, TLR signaling limits microbial invasion and prevents commensal organisms from breaching
the epithelial barrier, thereby maintaining gingival health.
• Periodontal health represents a dynamic state in which pro-inflammatory and anti-microbial activities
for control of infection are optimally balanced by anti-inflammatory mechanisms to prevent
unwarranted inflammation.
• This homeostasis is disrupted when pathogens present in dental plaque undermine the host defense
mechanism.

40. Disruption and penetration of the gingival
epithelial barrier by invasive bacteria or their cytotoxic
products
Invasion into deeper tissues
TLRs in cells such as macrophages, fibroblasts,
osteoblasts, osteoclasts and antigen-presenting cells
become activated
Various pro-inflammatory cytokines produced
Inflammation and immune cell infiltration
Infiltrated cells
(Eg:memory T-
cells)
Produce cytokines
Amplify the
inflammatory
reaction
Destruction of
connective tissue
and bone

41. Chronic stimulation of TLRs in periodontal tissues by bacterial PAMPs
Excessive production of pro-inflammatory mediators
Tissue destruction

42. • First cells to respond to PAMPs are the epithelial cells lining the sulcus.
Epithelial Cells
Intercellular adhesion molecule-1 (ICAM-1)
Lymphocyte function-associated antigen-1 (LFA-1)
Direct the attachment and migration of leucocytes towards the gingival sulcus.
Epithelial cells  produce matrix metalloproteinases (MMPs) in response to PAMPs, causing direct
damage to periodontal tissues.
When stimulated via TLRs, neutrophils exhibit increased chemotaxis  production of pro-inflammatory
cytokines [interleukin-1 (IL-1); interleukin-6 (IL-6); tumor necrosis factor-α (TNF-α)]
NEGATIVE EDGE

43. Toll-like receptor-mediated progression of periodontal disease

44. • IL-8 secreted by epithelial cells  stimulates the endothelial cells lining the blood vessels through
TLR-4 increased adhesion of monocytes
• exposed to PAMPs monocytes produce proinflammatory cytokines and differentiate into osteoclasts
upon direct stimulation with bacterial lipopolysaccharides with the help of RANKL.
• TLRs present on dendritic cells stimulated with PAMPs induce their maturation act as antigen-
presenting cells  produce cytokines and co-stimulatory molecules activate T-lymphocytes to
produce Th1 or Th2 immune response

45. Epithelial Barrier
Is Breached
Microorganisms And
Their Products Access
Gain To The Underlying
Connective Tissue
Directly Activate The
Cells Present There

46. • Once stimulated by PAMPs, gingival fibroblasts produce pro-inflammatory cytokines leading to
tissue destruction and bone resorption.
• Periodontal ligament fibroblasts, produce proteinases on TLR stimulation, resulting in direct
degradation of periodontal tissues.
• PAMPs entering the circulation via blood vessels in connective tissue lymphocytes move toward the
site of infection.
• In the presence of biological mediators, naïve T-cells differentiate and initiate a Th1 or Th2
immune response.

47. • TLRs on T cells act as type of co-stimulatory molecule.
• B lymphocytes are transformed into plasma cells, which produce antibodies against bacterial
antigens.
• Osteoblasts react to PAMPs through TLRs and produce biological mediators (MMPs, prostaglandin
E2) responsible for bone resorption.
• Osteoblasts, marrow stromal cells, and T and B cells express RANKL, which is essential for
activation of osteoclasts.
• RANKL in the presence of macrophage colony-stimulating factor (M-CSF) attaches to RANK
present on osteoclasts and osteoclast precursors, and activates them.

49. Evasion or subversion of Toll-like receptor (TLR)
activation by Porphyromonas gingivalis
P. gingivalis - lipid A phosphatase and deacylase activities - modify the lipid
A structure LPS.
These modifications - lipopolysaccharide molecules that can either evade or
actively antagonize TLR4 activation
Although the activation of the TLR2 ⁄ TLR1 - not antagonized at the TLR
receptor level, P. gingivalis instigates a molecular crosstalk between the
CXC-chemokine receptor 4 and TLR2 ⁄ 1.
Unlike CD14, which facilitates TLR2 ⁄ 1 activation by the pathogen -
suppresses TLR2 signaling.
Mechanistically, P. gingivalis uses its fimbriae to bind CXCR4 and induce
cyclic AMP-dependent protein kinase A (PKA) signaling, which in turn inhibits
the activation of nuclear factor-kappaB (NF-jB) activation.

50. Crosstalk pathways between (TLRs) and complement in Porphyromonas gingivalis
activated macrophages.
- TLR recognition of P. gingivalis is predominantly mediated by the TLR2 ⁄ TLR1
heterodimer (TLR2 ⁄ 1), aided by the CD14 co-receptor.
- This interaction induces phosphatidylinositol 3-kinase (PI3K)- dependent inside-out
signaling, which transactivates the high-affinity state of complement receptor-3 (CR3).
-Interestingly, P. gingivalis interacts with activated CR3 and induces (ERK1 ⁄ 2) signaling,
which in turn downregulates the expression of messenger RNA for cytokines of the
interleukin- 12 family .
-Moreover, P. gingivalis uses its gingipains to attack C5 and release biologically active
C5a.
Through its receptor (C5aR), C5a can activate PI3K and ERK1 ⁄ 2, which in turn
suppress critical transcription factors (the interferon regulatory factors 1 and 8; IRF-1
and -8), required for expression of cytokines of the interleukin-12 family.
- Intriguingly, inhibition of bioactive interleukin-12 though these mechanisms results in
impaired immune clearance of P. gingivalis in vivo suggesting that the pathogen exploits
TLR ⁄ complement

51. Role of virus in TLR’S
- Several lines of evidence link herpesviruses, especially human cytomegalovirus and Epstein-Barr virus to the
severity of periodontitis.
These evidences include:
• The detection of viral DNA in gingival tissue .
• The presence of higher frequency of viral DNA in periodontitis tissue than in healthy periodontal tissue .
• The detection of active human cytomegalovirus replication in periodontal tissue .
- Several studies demonstrate that the presence of subgingival human cytomegalovirus or Epstein-Barr virus-1
DNA is associated with an increased presence periodontopathic bacteria .
- The findings suggest that local immune responses against oral plaque bacteria could be suppressed as a
result of herpesvirus infection.

52. - More specifically, Toll-like receptors 2 and 9 have been demonstrated to sense herpesvirus-associated
molecules and initiate antiviral responses.
- A study done by Compton et al 2003 revealed that Recognition of human cytomegalovirus virions
by Toll-like receptor 2 and CD14 leads to cytokine production.
- Krug et al 2004 in his study model done on mouse revealed that recognition of DNA viruses
by Toll-like receptor 9 is required for interferon-a Production
- In a study done by Alexopoulou et al – 2004 showed that Toll-like receptor 3 has been shown to recognize
dsRNA , a product of viral replication.
- Yoneyama et al 2004 showed that Host cells also express cytoplasmic RNA helicases
that can recognize dsRNA via Toll-like receptor- independent mechanisms.
- The presence of mRNA expression of Toll-like receptors 2, 3 and 9 in human gingival epithelial cells and
fibroblasts may suggest the role of periodontal tissue in antiviral responses.

53. Subjects TLR Ligands Reference
CP patients TLR 8 & 9 upregulated Sahiingur et al (2013)
CP patients TLR4 Ozturk and Yildiz(2011)
CP patients
TLR2 & TLR4
Becerik et al(2011),
Ribeiro et al(2012)
Li et al (2014b),
Beklen et al (2014),
Duarte et al (2012)
CP patients TLR9 Chen et al(2014)
CP patients
TLR4 no change, TLR2 & TLR9 Wara-aswapati et al (2013)
Studies related to chronic periodontitis

54. Studies related to Aggressive periodontitis

55. TLR and Periimplantitis

56. TLR in CP with systemic diseases
objects stimulus effects Refs
RA mice and mice
with CP
Cathepsin K KO TLR4, TLR5,
TLR9 reduced;
bone loss
inhibited
Hao ei al(2015)
APCs withTLR2
deficiency.
P.gingivalis Th 17 induction
inhibited.
de aquino et
al(2014)
CP patientswith
DM
TLR2 and TLR4 in
periodontal tissue
dysregulated
Promsudthi et al
(2014)
Patients with both
CP and DM
TLR2, TLR4, TLR9
elevated than CP
alone
Rojo-Botello et al
(2012)
TLR2 has been suggested as a potential therapeutic target in
the treatment of Periodontal disease,RA,,DM

57. • Prathahini Parthiban, 2015 Studied the role of TLR in periodontal disease and relationship with
pre term labour.

58. TLR in association with Cardiac disease

60. Conclusion
• Toll-like receptor signaling at the dento-epithelial junction is critical in maintaining periodontal
health as well as in the progression of periodontitis.
• There are still gaps in our knowledge of the mechanisms by which TLRs maintain periodontal health
and what leads to bacterial immune evasion and disease progression.
• It is uncertain which specific signaling pathways need to be blocked to attenuate the pathology or
enhanced to promote host defense.
• Further investigations are required in this field to understand the initiation and progression of
periodontal disease and develop therapeutic interventions to control it.

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