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. 2023 Nov 19;12(22):2654. doi: 10.3390/cells12222654

Table 1.

Different PRRs, their ligands and functions in IBD and CRC.

Mediators Ligands Role in IBD REF Role in CRC REF
TLR-2 Lipoproteins
  • -

    extracellular pathogen immunity;

  • -

    mediates intestinal inflammation and its expression has been shown to be increased in macrophages of IBD patients;

  • -

    modulations of T-cells functions both directly, stimulating Th17 response, and indirectly, reducing the suppressive function of Tregs by promoting a shift toward IL-17 production;


[33]
  • -

    TLR2 -196 to -174 del/del homozygous genotypes are significantly associated with CRC (human study);


[61]
TLR-3 Viral ds-RNA
  • -

    antiviral immunity;
  • -

    TLR3 rs3775292 polymorphism, is significantly associated with rectal cancer (human study);


[62]
TLR-4 LPS
  • -

    extracellular pathogen immunity;

  • -

    causes tissue destruction and ulceration;

  • -

    mediates intestinal inflammation and its expression is increased in macrophages of IBD patients;

  • -

    over-expression of TLR4 is associated to increased inflammatory mediators, such as TNF-alpha, COX-2, and IL-12, with higher susceptibility to IBD;

  • -

    alterations in the TLR4 gene may predispose to Gram-negative bacteria infections and generic increased susceptibility to enteric infections;

  • -

    is increased in IBD patients and it may be considered as an active participant in IBD disease development;

  • -

    TLR4 deficient mice have decreased level of intestinal inflammation (animal study);

  • -

    TLR4 D299G and rs4986790 polymorphisms are associated with IBD (animal study);

[63]

[64]





[65]


[52]
  • -

    over-expression of TLR4 is associated to increased inflammatory mediators, such as TNF-alpha, COX-2, and IL-12, with higher susceptibility to colitis-associated CRC (human study);

  • -

    TLR4 rs11536898 polymorphism is associated with colon cancer (human study);

  • -

    TLR4 Asp299Gly, TLR4 Thr399Ile homozygous genotypes are significantly associated with CRC (human study);

  • -

    TLR4 Asp299Gly and Thr399Ile polymorphisms were significantly associated with concomitant KRAS gene mutations (human study);

  • -

    TLR4 expression may be linked to increase metastases (human study);

  • -

    TLR4 deficiency may prevent colitis-associated neoplasia (animal study);
[66]
[67]
[62]

[61]

[61]


[68]


[65]
TLR-6 Lipoproteins
  • -

    TLR6 rs5743810 polymorphism is associated with IBD (human study);
[60]
  • -

    TLR6 rs3796508 has a crucial role as a protective factor against colorectal cancer;

  • -

    TLR6-deficient mice presented higher risk of developing cancer and a worse overall outcome;
[60]
TLR-9 Microbial ss-RNA
  • -

    antiviral immunity;

  • -

    TLR9 rs352140 polymorphism is associated with IBD (human study);
[58]
  • -

    TLR9 T1237C and T1486C homozygous genotypes are significantly associated with CRC (human study);
[61]
NOD2 Bacterial peptidoglycan (PGN) fragments
  • -

    NOD2 activates the NF-kB and MAPK signaling axis in response to bacterial MDP favoring the production of inflammatory mediators (animal study);

  • -

    Dysfunctional NOD2 signaling may contribute to the pathogenesis of Crohn's disease;
[69]
  • -

    NOD2 is able to suppress inflammation and tumorigenesis in the colon downregulating the TLR signaling pathways (animal study);

  • -

    NOD2 polymorphisms increase the risk of CRC;

  • -

    NOD2 R702W, G908R, and 3020insC variants may be associated in higher CRC susceptibility in Caucasians (human study);
[69]



[70]
CARD9 Various PAMPs and DAMPs
  • -

    triggers the activation of NF-κB and STAT3, inducing the production of pro-inflammatory cytokines;

  • -

    dysregulation of CARD9 signaling can disrupt immune responses and contribute to the uncontrolled IBD related inflammation;
[71]
  • -

    highly expressed in CRC tumor tissue;

  • -

    highly expressed in tumor-infiltrating macrophages rather than cancer cells and is associated with CRC tumor metastasis and advanced histopathologic stage (animal study);

  • -

    dysregulated CARD9 is a critical risk factor in the progression of CRC;

[72]


[73]
CARD15 Various PAMPs and DAMPs
  • -

    CARD15 mutations are associated with higher susceptibility to CD (animal study);

  • -

    mutations in the CARD15 gene have been linked to an increased risk of developing Crohn's disease.
[74]
  • -

    CARD15 mutations are associated with higher susceptibility to CRC;

  • -

    the CARD15 R702W variant may be a predisposing factor to sporadic CRC (human study).

[75]