The epidemiology of oral candidal carriage and infections in diabetic patients is complex and includes species which have not been previously reported in this group of patients. The development of oral candidosis in insulin-treated diabetes mellitus patients is not the result of a single entity, but rather, a combination of risk factors.

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Induction of endotoxin tolerance leads to a reduced inflammatory response after repeated challenge by LPS and is important for resolution of inflammation and prevention of tissue damage. Enterobacterial LPS is recognized by the TLR4 signaling complex, whereas LPS of some non-enterobacterial organisms is capable of signaling independently of TLR4 utilizing TLR2-mediated signal transduction instead. In this study we report that Porphyromonas gingivalis LPS, a TLR2 agonist, fails to induce a fully endotoxin tolerant state in a human monocytic cell line (THP-1) and mouse bone marrow-derived macrophages. In contrast to significantly decreased production of human IL-8 and TNF-␣ and, in mice, keratinocyte-derived cytokine (KC), macrophage inflammatory protein-2 (MIP-2), and TNF-␣ after repeated challenge with Escherichia coli LPS, cells repeatedly exposed to P. gingivalis LPS responded by producing less TNF-␣ but sustained elevated secretion of IL-8, KC, and MIP-2. Furthermore, in endotoxin-tolerant cells, production of IL-8 is controlled at the signaling level and correlates well with NF-B activation, whereas TNF-␣ expression is blocked at the gene transcription level. Interferon ␤ plays an important role in attenuation of chemokine expression in endotoxin-tolerized cells as shown in interferon regulatory factor-3 knock-out mice. In addition, human gingival fibroblasts, commonly known not to display LPS tolerance, were found to be tolerant to repeated challenge by LPS if pretreated with interferon ␤. The data suggest that the inability of the LPS-TLR2 complex to induce full endotoxin tolerance in monocytes/macrophages is related to diminished production of interferon ␤ and may partly explain the involvement of these LPS isoforms in the pathogenesis of chronic inflammatory diseases.Detection of pathogen-associated molecular patterns by Toll-like receptors (TLRs) 2 expressed on innate immune cells triggers a robust and essential inflammatory reaction. Inflammation as a well coordinated process that comprises increased vascular permeability, migration of polymorphonuclear leukocytes, monocytes, and lymphocytes into affected tissues, and activation of cells to secrete inflammatory mediators is essential for host defense (1). If it is well controlled and resolved in a timely manner, it benefits the host by elimination of the invading pathogen. Otherwise, prolonged or excessive inflammation leads to chronicity and tissue damage (2).Toll-like receptors represent a family of evolutionarily highly conserved transmembrane molecules that act as pathogen recognition receptors. To date, 13 mammalian TLRs have been identified, and each appears to be required for responses to a different class of infectious pathogen (3). Almost immediately after microbes invade, microbial products signal through TLRs, broadly distributed on immune cells, activating these cells to produce proinflammatory cytokines, interferons, histamine, and antimicrobial peptides (4). Toll-like receptor signaling represents a principal molecular pathway for host in...

Porphyromonas gingivalis produces different LPS isoforms with significant structural variations of their lipid A and O-antigen moieties that can affect its pro-inflammatory and bone-resorbing potential. We show here, for the first time, that P. gingivalis LPS isolated from W83 strain is highly sialylated and possesses significantly reduced inflammatory potential compared with less sialylated ATCC 33277 strain LPS. Nevertheless, the reduction in the endotoxin activity is not mediated by the presence of sialic acid LPS moieties as the sialic acid-free LPS produced by the mutant W83 strain exhibits a similar inflammatory potential to the wild type strain. Furthermore, our findings suggest that the interaction between the sialic acid LPS moieties and the inhibitory CD33 receptor is prevented by endogenously expressed sialic acid on the surface of THP-1 cells that cannot be out-competed by sialic acid containing P. gingivalis LPS. The present study also highlights the importance of endogenous sialic acid as a ‘self-associated molecular pattern’ and CD33 receptors in modulation of innate immune response as human gingival fibroblasts, which do not express CD33 receptors, and desialylated THP-1 cells have both been found to have much higher spontaneous IL-8 production than naïve THP-1 cells.