S. Y. Fukada, Tarcília Aparecida Silva, G. Garlet, Adalberto Luiz Rosa, J. S. D. Silva, Fernando Q. Cunha
{"title":"Factors involved in the T helper type 1 and type 2 cell commitment and osteoclast regulation in inflammatory apical diseases.","authors":"S. Y. Fukada, Tarcília Aparecida Silva, G. Garlet, Adalberto Luiz Rosa, J. S. D. Silva, Fernando Q. Cunha","doi":"10.1111/j.1399-302X.2008.00469.x","DOIUrl":"https://doi.org/10.1111/j.1399-302X.2008.00469.x","url":null,"abstract":"INTRODUCTION\u0000Periapical chronic lesion formation involves activation of the immune response and alveolar bone resorption around the tooth apex. However, the overall roles of T helper type 1 (Th1), Th2, and T-regulatory cell (Treg) responses and osteoclast regulatory factors in periapical cysts and granulomas have not been fully determined. This study aimed to investigate whether different forms of apical periodontitis, namely cysts and granulomas, show different balances of Th1, Th2 regulators, Treg markers, and factors involved in osteoclast chemotaxis and activation.\u0000\u0000\u0000METHODS\u0000Gene expression of these factors was assessed using quantitative real-time polymerase chain reaction, in samples obtained from healthy gingiva (n = 8), periapical granulomas (n = 20), and cysts (n = 10).\u0000\u0000\u0000RESULTS\u0000Periapical cysts exhibited a greater expression of GATA-3, while a greater expression of T-bet, Foxp3, and interleukin-10 (IL-10) was seen in granulomas. The expression of interferon-gamma, IL-4, and transforming growth factor-beta was similar in both lesions. Regarding osteoclastic factors, while the expression of SDF-1alpha/CXCL12 and CCR1 was higher in cysts, the expression of RANKL was significantly higher in granulomas. Both lesions exhibited similar expression of CXCR4, CKbeta8/CCL23, and osteoprotegerin, which were significantly higher than in control.\u0000\u0000\u0000CONCLUSION\u0000Our results showed a predominance of osteoclast activity in granulomas that was correlated with the Th1 response. The concomitant expression of Treg cell markers suggests a possible suppression of the Th1 response in granulomas. On the other hand, in cysts the Th2 activity is augmented. The mechanisms of periradicular lesion development are still not fully understood but the imbalance of immune and osteoclastic cell activity in cysts and granulomas seems to be critically regulated by Treg cells.","PeriodicalId":19630,"journal":{"name":"Oral microbiology and immunology","volume":"24 1 1","pages":"25-31"},"PeriodicalIF":0.0,"publicationDate":"2009-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-302X.2008.00469.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62843701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ann R. Griswold, Marcelle M. Nascimento, Robert A. Burne
{"title":"Distribution, regulation and role of the agmatine deiminase system in mutans streptococci.","authors":"Ann R. Griswold, Marcelle M. Nascimento, Robert A. Burne","doi":"10.1111/j.1399-302X.2008.00459.x","DOIUrl":"https://doi.org/10.1111/j.1399-302X.2008.00459.x","url":null,"abstract":"The agmatine deiminase system (AgDS) was identified in seven strains of mutans streptococci. Genes encoding the AgDS of Streptococcus rattus FA-1 were sequenced and found to share homology with the agu genes of Streptococcus mutans UA159. With the exception of Streptococcus sobrinus, the AgDS of mutans streptococci appear to be sensitive to carbohydrate catabolite repression. Agmatine inhibited bacterial growth, suggesting that the AgDS degrades a deleterious substance into useful compounds.","PeriodicalId":19630,"journal":{"name":"Oral microbiology and immunology","volume":"24 1 1","pages":"79-82"},"PeriodicalIF":0.0,"publicationDate":"2009-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-302X.2008.00459.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62843514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cardoso Cr, Garlet Gp, Crippa Ge, Rosa Al, Júnior Wm, R. Ma, Silva Js Evidence
{"title":"Evidence of the presence of T helper type 17 cells in chronic lesions of human periodontal disease.","authors":"Cardoso Cr, Garlet Gp, Crippa Ge, Rosa Al, Júnior Wm, R. Ma, Silva Js Evidence","doi":"10.1111/j.1399-302X.2008.00463.x","DOIUrl":"https://doi.org/10.1111/j.1399-302X.2008.00463.x","url":null,"abstract":"INTRODUCTION\u0000Periodontal disease is a chronic inflammation of the attachment structures of the teeth, triggered by potentially hazardous microorganisms and the consequent immune-inflammatory responses. In humans, the T helper type 17 (Th17) lineage, characterized by interleukin-17 (IL-17) production, develops under transforming growth factor-beta (TGF-beta), IL-1beta, and IL-6 signaling, while its pool is maintained by IL-23. Although this subset of cells has been implicated in various autoimmune, inflammatory, and bone-destructive conditions, the exact role of T lymphocytes in chronic periodontitis is still controversial. Therefore, in this study we investigated the presence of Th17 cells in human periodontal disease.\u0000\u0000\u0000METHODS\u0000Gingival and alveolar bone samples from healthy patients and patients with chronic periodontitis were collected and used for the subsequent assays. The messenger RNA expression for the cytokines IL-17, TGF-beta, IL-1beta, IL-6, and IL-23 in gingiva or IL-17 and receptor activator for nuclear factor-kappaB ligand in alveolar bone was evaluated by real-time polymerase chain reaction. The production of IL-17, TGF-beta, IL-1beta, IL-6, and IL-23 proteins was evaluated by immunohistochemistry and the presence of Th17 cells in the inflamed gingiva was confirmed by immunofluorescence confocal microscopy for CD4 and IL-17 colocalization.\u0000\u0000\u0000RESULTS\u0000Our data demonstrated elevated levels of IL-17, TGF-beta, IL-1beta, IL-6, and IL-23 messenger RNA and protein in diseased tissues as well as the presence of Th17 cells in gingiva from patients with periodontitis. Moreover, IL-17 and the bone resorption factor RANKL were abundantly expressed in the alveolar bone of diseased patients, in contrast to low detection in controls.\u0000\u0000\u0000CONCLUSION\u0000These results provided strong evidence for the presence of Th17 cells in the sites of chronic inflammation in human periodontal disease.","PeriodicalId":19630,"journal":{"name":"Oral microbiology and immunology","volume":"24 1 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2009-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-302X.2008.00463.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62843547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toll-like receptors 2 and 5 in human gingival epithelial cells co-operate with T-cell cytokine interleukin-17.","authors":"A. Beklen, T. Sorsa, Y. Konttinen","doi":"10.1111/j.1399-302X.2008.00473.x","DOIUrl":"https://doi.org/10.1111/j.1399-302X.2008.00473.x","url":null,"abstract":"BACKGROUND/AIM\u0000Periodontitis begins as the result of perturbation of the gingival epithelial cells caused by subgingival bacteria interacting with the epithelial cells via pattern recognition receptors. Toll-like receptors (TLRs) have been shown to play an important role in the recognition of periodontal pathogens so we have studied the interaction of TLR ligands with TLR2 and TLR5 for cytokine production in the cultures of gingival epithelial cells.\u0000\u0000\u0000METHODS\u0000Immunohistochemistry was used for the localization of TLR2 and TLR5 in tissue specimens. Enzyme-linked immunosorbent assays were performed to detect the levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), released from gingival epithelial cell cultures following stimulation with TLR ligand alone or in combination with IL-17.\u0000\u0000\u0000RESULTS\u0000Both TLR2 and TLR5 were increased in periodontitis (2128 +/- 159 vs. 449 +/- 59 and 2456 +/- 297 vs. 679 +/- 103, respectively, P < 0.001) including gingival epithelial cells that stained strongly. Cultured gingival epithelial cells stimulated with their respective ligands (HKLM, a TLR2 ligand that is also found in Porphyromonas gingivalis, and flagellin, a TLR5 ligand that is also found in Treponema denticola) produced both IL-1beta and TNF-alpha. To mimic T-cell help, IL-17 was added. This further greatly enhanced TLR ligand-induced IL-1beta (P < 0.001) and TNF-alpha (P < 0.01) production.\u0000\u0000\u0000CONCLUSIONS\u0000These findings show how pathogen-associated molecular patterns, shared by many different periodontopathogenic bacteria, stimulate the resident gingival epithelial cells to inflammatory responses in a TLR-dependent manner. This stimulation may be particularly strong in periodontitis and when T helper type 17 cells provide T-cell help in intercellular cooperation.","PeriodicalId":19630,"journal":{"name":"Oral microbiology and immunology","volume":"24 1 1","pages":"38-42"},"PeriodicalIF":0.0,"publicationDate":"2009-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-302X.2008.00473.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62843833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Nomura, K. Nakano, H. Nemoto, T. Mukai, H. Hata, Koichi Toda, H. Yoshioka, K. Taniguchi, Atsuo Amano, Takashi Ooshima
{"title":"Molecular analyses of bacterial DNA in extirpated heart valves from patients with infective endocarditis.","authors":"R. Nomura, K. Nakano, H. Nemoto, T. Mukai, H. Hata, Koichi Toda, H. Yoshioka, K. Taniguchi, Atsuo Amano, Takashi Ooshima","doi":"10.1111/j.1399-302X.2008.00474.x","DOIUrl":"https://doi.org/10.1111/j.1399-302X.2008.00474.x","url":null,"abstract":"BACKGROUND/AIMS\u0000Infective endocarditis (IE) is caused by a microbial infection of the endothelial surface of the heart. Although blood culture examinations are commonly used to determine the associated bacterial species, molecular techniques, which enable rapid identification of targeted bacterial species, have recently been applied in clinical cases.\u0000\u0000\u0000METHODS\u0000Nine heart valve specimens from IE patients (six subacute cases and three acute cases) were extirpated and collected, then bacterial DNA was extracted. Bacterial species in the specimens were determined by two different molecular methods and the results were compared with those from a conventional blood culture technique. In addition, a comparison between the two molecular methods was carried out using known numbers of six streptococcal species.\u0000\u0000\u0000RESULTS\u0000The conventional blood culture method revealed the bacterial species in eight cases, while one was found to be negative. Multiple species were identified in most of the cases by both molecular methods; however, those specified by one method were not always consistent with those specified by the other. Furthermore, the species determined by the blood culture technique were not always identified by the molecular methods. We also found that the two molecular methods used in the present study were extremely sensitive to detect from 1 to 100 cells of individual oral streptococcal species.\u0000\u0000\u0000CONCLUSION\u0000Our results suggest that species specified by molecular methods may have disseminated incidentally into the bloodstream, so interpretation of such results should be carefully undertaken in clinical situations.","PeriodicalId":19630,"journal":{"name":"Oral microbiology and immunology","volume":"13 1","pages":"43-9"},"PeriodicalIF":0.0,"publicationDate":"2009-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-302X.2008.00474.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62843416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nitric oxide production by a human osteoblast cell line stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide.","authors":"W. Sosroseno, P. Bird, G. Seymour","doi":"10.1111/j.1399-302X.2008.00475.x","DOIUrl":"https://doi.org/10.1111/j.1399-302X.2008.00475.x","url":null,"abstract":"BACKGROUND/AIM\u0000Human osteoblasts induced by inflammatory stimuli express an inducible nitric oxide synthase (iNOS). The aim of the present study was to test the hypothesis that Aggregatibacter actinomycetemcomitans lipopolysaccharide stimulates the production of nitric oxide (NO) by a human osteoblast-like cell line (HOS cells).\u0000\u0000\u0000METHODS\u0000Cells were stimulated directly with A. actinomycetemcomitans lipopolysaccharide or pretreated with the following l-NIL (an iNOS inhibitor), anti-CD14, Toll-like receptor 2 (TLR2), or TLR4 antibody before stimulation with A. actinomycetemcomitans lipopolysaccharide. The role of the cyclic nucleotides was assessed by pretreating the cells with the following; ODQ (a guanylyl cyclase inhibitor); SQ22536 (an adenylyl cyclase inhibitor); db-cAMP (a cyclic adenosine monophosphate analog); br-cGMP (a cyclic guanosine monophosphate analog); forskolin (an adenylyl cyclase activator), IBMX [a non-specific phosphodiesterase (PDE) inhibitor], or KT5720 [a protein kinase A (PKA) inhibitor]. The cells were also preincubated with genistein [a protein tyrosine kinase (PTK) inhibitor], bisindolylmaleimide [a protein kinase C (PKC) inhibitor], BPB [a phospholipase A2 (PLA2) inhibitor], and NDGA (a lipoxygenase inhibitor). The iNOS activity and nitrite production in the cell cultures were determined spectrophotometrically.\u0000\u0000\u0000RESULTS\u0000The results showed that A. actinomycetemcomitans lipopolysaccharide stimulated both iNOS activity and nitrite production by HOS cells; this was reduced by l-NIL, anti-CD14, or anti-TLR4 antibody, SQ22536, KT5720, genistein, bisindolylmaleimde, BPB, and NDGA, but was enhanced by db-cAMP, IBMX, and forskolin.\u0000\u0000\u0000CONCLUSION\u0000These results therefore suggest that A. actinomycetemcomitans lipopolysaccharide may induce the production of NO by HOS cells via a CD14-TLR4 molecule complex, a cAMP-PKA pathway, as well as by a PTK, PKC, PLA2, and lipoxygenase-dependent mechanism.","PeriodicalId":19630,"journal":{"name":"Oral microbiology and immunology","volume":"24 1 1","pages":"50-5"},"PeriodicalIF":0.0,"publicationDate":"2009-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-302X.2008.00475.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62843473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of stereological principles for quantification of bacteria in intact dental biofilms.","authors":"I. Dige, J. Nyengaard, M. Kilian, B. Nyvad","doi":"10.1111/j.1399-302X.2008.00482.x","DOIUrl":"https://doi.org/10.1111/j.1399-302X.2008.00482.x","url":null,"abstract":"INTRODUCTION\u0000Quantative confocal laser scanning microscopy (CLSM) in combination with fluorescent in situ hybridization (FISH) may help to increase our knowledge about biofilm formation. The purpose of this study was to develop and evaluate a stereological method for quantification of bacteria in intact biofilm. The method was applied in a quantitative study of the proportion of streptococci relative to other bacteria in initial in-situ-grown dental biofilms as a function of time.\u0000\u0000\u0000METHODS\u0000Biofilms were collected on standardized glass slabs mounted in intra-oral appliances and worn by 10 individuals for 6, 12, 24, and 48 h. Biofilms were analysed using CLSM. Quantification of bacteria labelled with 16S ribosomal RNA oligonucleotide probes was performed with stereological tools: the unbiased counting frame and the two-dimensional fractionator.\u0000\u0000\u0000RESULTS\u0000Results showed a notable increase in the total number of bacteria and streptococci over time, with a considerable inter-individual variation at each time-point. After 48 h there was a 12.5-fold difference between individuals in the total number of bacteria and a 12.6-fold difference in the number of streptococci. The number of streptococci exceeded that of other bacteria and over the examination period there was a relatively constant relationship between the number of streptococci and other bacteria (streptococci vs. non-streptococci: median 15.2; minimum 1.0; maximum 89.3).\u0000\u0000\u0000CONCLUSION\u0000The study demonstrates that the combined use of FISH and stereology is a relevant and reliable tool for obtaining unbiased information about the numerical contributions of specific bacterial populations during early biofilm formation.","PeriodicalId":19630,"journal":{"name":"Oral microbiology and immunology","volume":"24 1 1","pages":"69-75"},"PeriodicalIF":0.0,"publicationDate":"2009-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-302X.2008.00482.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62843563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Stathopoulou, M. Benakanakere, J. Galicia, D. Kinane
{"title":"The host cytokine response to Porphyromonas gingivalis is modified by gingipains.","authors":"P. Stathopoulou, M. Benakanakere, J. Galicia, D. Kinane","doi":"10.1111/j.1399-302X.2008.00467.x","DOIUrl":"https://doi.org/10.1111/j.1399-302X.2008.00467.x","url":null,"abstract":"BACKGROUND/AIMS\u0000Clinical studies indicate that primary proinflammatory cytokines, such as interleukin-1beta (IL-1beta) are elevated in the gingival crevice around teeth with periodontitis but the secondary cytokines and chemokines, IL-6 and IL-8, are not. The human gingival epithelial cells (HGECs) lining the gingival sulcus respond to perturbation by microbes of dental plaque by releasing a wide range of cytokines. Porphyromonas gingivalis, a putative periodontal pathogen, possesses numerous virulence factors some of which directly impact on the host response. In the present study, we sought to determine how P. gingivalis influences the inflammatory cytokine responses.\u0000\u0000\u0000METHODS\u0000HGECs were challenged with P. gingivalis and other putative periodontal pathogens, and the resultant production of IL-1beta, IL-6, and IL-8 was assayed by enzyme-linked immunosorbent assay (ELISA). Culture supernatants and recombinant human cytokines were challenged with live P. gingivalis wild-type and gingipain-deficient strains and the resultant cytokine profile was assessed by ELISA and Western blot.\u0000\u0000\u0000RESULTS\u0000We show here that primary HGECs challenged with live P. gingivalis result in high levels of IL-1beta but not the related secondary cytokines IL-6 and IL-8. We further demonstrate that cytokine response differences are the result of the action of P. gingivalis proteases, with lysine gingipain being the most effective.\u0000\u0000\u0000CONCLUSION\u0000We conclude that P. gingivalis, through lysine gingipain, can subvert the protective host proinflammatory response by direct cytokine degradation. Changes in the crevicular cytokine profile have consequences in periodontal disease pathogenesis that should be considered in the development of diagnostic and therapeutic modalities.","PeriodicalId":19630,"journal":{"name":"Oral microbiology and immunology","volume":"57 1","pages":"11-7"},"PeriodicalIF":0.0,"publicationDate":"2009-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-302X.2008.00467.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62843598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between Bifidobacteriaceae and the clinical severity of root caries lesions.","authors":"M. Mantzourani, Michael R. Fenlon, David Beighton","doi":"10.1111/j.1399-302X.2008.00470.x","DOIUrl":"https://doi.org/10.1111/j.1399-302X.2008.00470.x","url":null,"abstract":"BACKGROUND/AIMS\u0000The isolation of members of the family Bifidobacteriaceae (bifids) from oral samples has been sporadic and a recent cloning study has suggested that they are not detectable in root caries lesions.\u0000\u0000\u0000METHODS\u0000To better understand the presence of bifids in root caries we obtained clinical samples (15 of each) from sound exposed root surfaces, leathery remineralizing root lesions, and soft active root lesions. We investigated each for the presence of bifids using a mupirocin-containing selective medium and identified the isolates using 16S recombinant RNA sequencing.\u0000\u0000\u0000RESULTS\u0000The proportion of bifids, as a percentage of the total anaerobic count, was significantly related to the clinical status of the sites sampled, being 7.88 +/- 1.93 in the infected dentine from soft lesions, 1.61 +/- 0.91 in leathery lesions, and 0.05 +/- 0.39 in plaque from sound exposed root surfaces. Bifids were isolated from all soft lesions, 13 of 15 leathery lesions, and five of the plaque samples. Bifidobacterium dentium was isolated from four of the plaque samples, from 13 samples from leathery lesions, and from 12 of the 15 samples of infected dentine from the soft active lesions. Parascardovia denticolens and Scardovia genomospecies C1 were each isolated from samples associated with all three clinical conditions whereas Scardovia inopicata and Bifidobacterium subtile were both isolated from the infected dentine of the leathery and soft lesions. Bifidobacterium breve was isolated from the infected dentine of soft root caries lesions.\u0000\u0000\u0000CONCLUSION\u0000Bifids may be routinely isolated from root caries lesions using appropriate cultural methods.","PeriodicalId":19630,"journal":{"name":"Oral microbiology and immunology","volume":"24 1 1","pages":"32-7"},"PeriodicalIF":0.0,"publicationDate":"2009-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-302X.2008.00470.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62843770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Farah, J. Saunus, Y. Hu, A. Kazoullis, R. Ashman
{"title":"Gene targeting demonstrates that inducible nitric oxide synthase is not essential for resistance to oral candidiasis in mice, or for killing of Candida albicans by macrophages in vitro.","authors":"C. Farah, J. Saunus, Y. Hu, A. Kazoullis, R. Ashman","doi":"10.1111/j.1399-302X.2008.00462.x","DOIUrl":"https://doi.org/10.1111/j.1399-302X.2008.00462.x","url":null,"abstract":"INTRODUCTION\u0000Oral candidiasis is caused by opportunistic infections with the yeast Candida albicans. Previous studies have demonstrated important roles for innate immunity and T helper type 1-mediated inflammatory reactions in recovery from infection, with macrophages and neutrophils as key effector cells. Both effector cell types use the inducible isoform of nitric oxide synthase (iNOS) to generate candidacidal molecules, but it is not clear whether nitric oxide (NO) is an absolute requirement for candidacidal effector activity.\u0000\u0000\u0000METHODS\u0000In this study we directly investigated the role of iNOS-derived NO in resistance to murine experimental oral candidiasis, using iNOS knockout mice.\u0000\u0000\u0000RESULTS\u0000Knockout mice were no more susceptible to oral candidiasis than wild-type controls. Bone marrow-derived macrophages from the knockout mice killed C. albicans yeasts efficiently in vitro, and were still able to produce nitrites in an iNOS-independent manner, albeit less efficiently than wild-type controls. There were no significant differences in local mucosal production of interleukins 6, 12, 17A, or 23, interferon-gamma, or transforming growth factor-beta 24 h after oral challenge with C. albicans.\u0000\u0000\u0000CONCLUSION\u0000These data suggest that iNOS-derived NO is not required for resistance to oral candidiasis in vivo, and that bone marrow-derived macrophages may have iNOS-independent means of generating reactive nitrogen species.","PeriodicalId":19630,"journal":{"name":"Oral microbiology and immunology","volume":"24 1 1","pages":"83-8"},"PeriodicalIF":0.0,"publicationDate":"2009-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-302X.2008.00462.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62843541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}