Table.
Newly Recognized Actions of Host-Derived Danger Signal Molecules and Putative Cellular Innate Responses with Important Pathophysiologic Roles During Epithelial Cell and Bacteria Interaction.
| Endogenous Danger Molecule | Newly Characterized Innate Mechanisms for Epithelial Cell and Bacteria Interaction | Oro- and Aerodigestive Bacteria | Cell Type |
|---|---|---|---|
| Extracellular Adenosine | A) Disrupted purine homeostasis [1, 2] B) CD73 expression and activity [1, 2] C) Regulation of cellular ROS [1] D) Modulation of NOX activity [1] E) Regulation of proinflammatory IL-6 via activation of CD73 [1] |
Porphyromonas gingivalis(A to E)Salmonella species(A, B) | Primary gingival epithelial cellsIntestinal epithelial cells |
| A) Adenosine receptor activation modulating host resistance to infection [3 to 5] B) cAMP dependent CREB activation [3] C) Regulation of proinflammatory IL-6 via adenosine receptor [4] |
Streptococcus pneumoniae (A)Clostridium difficile (A, C)Porphyromonas gingivalis (A, B) | Pulmonary epithelial cellsCecum epithelial cellsPrimary gingival epithelial cells | |
| A) Pannexin-1 mediated release of bacterial effector [6] B) eATP-evoked ROS modulation by CD73 [1] C) NLRP3 inflammasome activation [7, 8] D) Modulation of proinflammatory cytokine secretion (IL-1β and/or IL-6) [1, 7] |
Porphyromonas gingivalis (A to D) | Primary gingival epithelial cells | |
| Fusobacterium nucleatuma (C, D) | Primary gingival epithelial cells | ||
| ExtracellularATP | A) Mitochondria and NOX2-generated ROS [9] B) Induction/activation of NOX2 [9] C) Activation of bactericidal NOX2/MPO pathway [9] D) Induction/production of glutathione [9] |
Porphyromonas gingivalis (A to D) | Primary gingival epithelial cells |
| A) Cas-1 and/or Cas-4 activation [8, 10] B) Induction of eATP release [6, 11] C) Infection leading to induction of host danger signals (e.g., eATP) and pyroptosis [10] D) Induction of selective autophagy [12, 13] |
Porphyromonas gingivalis (A, B, D)Aggregatibacter actinomycetemcomitans (B, D)Tannerella forsythia (A, C)Treponema denticola (A, C) | Primary gingival epithelial cellsPeriodontal fibroblasts gingival epithelial cell linebMacrophagesbMacrophagesb | |
| HMGB1 | A) Infection leading to initiation of multiple host danger signals [7, 14] B) Cas-1 activation [14] C) IL-1β, HMGB1 interplay [14] |
Fusobacterium nucleatum (A, B)Porphyromonas gingivalis (A to C) | Primary gingival epithelial cellsPrimary gingival epithelial cells |
| Calprotectin | A) p38, JNK MAPK, and NF-κB signaling induces Calprotectin via RAGE, TLR2 [15] B) Modulation of ROS [16] C) IL-1α regulation [17] |
Porphyromonas gingivalis (A)Salmonella typhimurium (B)Listeria monocytogenes (C) | Gingival epithelial cell lineIntestinal epithelial cellsBuccal epithelial cell line |
Table references are cited by numbers in brackets; see Appendix.
cAMP, cyclic AMP; Cas, caspase; CREB, cAMP response element-binding protein; eATP, extracellular ATP; HMGB1, high mobility group box 1 protein; JNK, c-Jun NH2-terminal kinase; MAPK, mitogen-activated protein kinase; MPO, myeloperoxidase; NF-κB, nuclear factor kappa B; NOX, NADPH oxidase; NOX2, NADPH oxidase 2; RAGE, receptor for advanced glycation end products; ROS, reactive oxygen species; TLR2, toll-like receptor 2.
F. nucleatum does not require eATP signal to activate NLRP3 inflammasome and subsequent IL-1β secretion, which is contrary to P. gingivalis, which needs ATP as a secondary stimulus.
Macrophages and fibroblasts were included in the table since their related mechanisms were specifically highlighted in this review as potentially shared but differentially modulated innate machineries reserved in epithelial cells.