scholarly journals Identifying a Role for Toll-Like Receptor 3 in the Innate Immune Response to Chlamydia muridarum Infection in Murine Oviduct Epithelial Cells

2011 ◽  
Vol 80 (1) ◽  
pp. 254-265 ◽  
Author(s):  
Wilbert A. Derbigny ◽  
LaTasha R. Shobe ◽  
Jasmine C. Kamran ◽  
Katherine S. Toomey ◽  
Susan Ofner
Keyword(s):  
Epithelial Cells ◽  
Toll Like Receptor ◽  
Content Type ◽  
Immune Modulators ◽  
Chlamydia Muridarum ◽  
Major Cell Type ◽  
Genital Tract Infections ◽  
Inflammatory Cytokine Response ◽  
Tract Infections ◽  
Cell Data

ABSTRACTBecause epithelial cells are the major cell type productively infected withChlamydiaduring genital tract infections, the overall goal of our research was to understand the contribution of infected epithelial cells to the host defense. We previously showed that Toll-like receptor 3 (TLR3) is the critical pattern recognition receptor in oviduct epithelial (OE) cells that is stimulated duringChlamydiainfection, resulting in the synthesis of beta interferon (IFN-β). Here, we present data that implicates TLR3 in the expression of a multitude of other innate-inflammatory immune modulators including interleukin-6 (IL-6), CXCL10, CXCL16, and CCL5. We demonstrate thatChlamydia-induced expression of these cytokines is severely disrupted in TLR3-deficient OE cells, whereasChlamydiareplication in the TLR3-deficient cells is more efficient than in wild-type OE cells. Pretreatment of the TLR3-deficient OE cells with 50 U of IFN-β/ml prior to infection diminishedChlamydiareplication and restored the ability ofChlamydiainfection to induce IL-6, CXCL10, and CCL5 expression in TLR3-deficient OE cells; however, CXCL16 induction was not restored by IFN-β preincubation. Our findings were corroborated in pathway-focused PCR arrays, which demonstrated a multitude of different inflammatory genes that were defectively regulated duringChlamydiainfection of the TLR3-deficient OE cells, and we found that some of these genes were induced only when IFN-β was added prior to infection. Our OE cell data implicate TLR3 as an essential inducer of IFN-β and other inflammatory mediators by epithelial cells duringChlamydiainfection and highlight the contribution of TLR3 to the inflammatory cytokine response.

scholarly journals The Genital Tract Virulence Factor pGP3 Is Essential for Chlamydia muridarum Colonization in the Gastrointestinal Tract

2017 ◽  
Vol 86 (1) ◽  
Author(s):  
Lili Shao ◽  
Tianyuan Zhang ◽  
Jose Melero ◽  
Yumeng Huang ◽  
Yuanjun Liu ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Virulence Factor ◽  
Genital Tract ◽  
Gi Tract ◽  
Content Dissemination ◽  
Content Type ◽  
Chlamydia Muridarum ◽  
Colonization Factor ◽  
Genital Tract Infections ◽  
Tract Infections

ABSTRACTThe cryptic plasmid is essential forChlamydia muridarumdissemination from the genital tract to the gastrointestinal (GI) tract. Following intravaginal inoculation, aC. muridarumstrain deficient in plasmid-encoded pGP3 or pGP4 but not pGP5, pGP7, or pGP8 failed to spread to the mouse gastrointestinal tract, although mice infected with these strains developed productive genital tract infections. pGP3- or pGP4-deficient strains also failed to colonize the gastrointestinal tract when delivered intragastrically. pGP4 regulates pGP3, while pGP3 does not affect pGP4 expression, indicating that pGP3 is critical forC. muridarumcolonization of the gastrointestinal tract. Mutants deficient in GlgA, a chromosome-encoded protein regulated by pGP4, also consistently colonized the mouse gastrointestinal tract. Interestingly,C. muridarumcolonization of the gastrointestinal tract positively correlated with pathogenicity in the upper genital tract. pGP3-deficientC. muridarumstrains did not induce hydrosalpinx or spread to the GI tract even when delivered to the oviduct by intrabursal inoculation. Thus, the current study not only has revealed that pGP3 is a novel chlamydial colonization factor in the gastrointestinal tract but also has laid a foundation for investigating the significance of gastrointestinalChlamydia.

scholarly journals PmpG303-311, a Protective Vaccine Epitope That Elicits Persistent Cellular Immune Responses in Chlamydia muridarum-Immune Mice

2012 ◽  
Vol 80 (6) ◽  
pp. 2204-2211 ◽  
Author(s):  
Raymond M. Johnson ◽  
Hong Yu ◽  
Micah S. Kerr ◽  
James E. Slaven ◽  
Karuna P. Karunakaran ◽  
...  
Keyword(s):  
T Cell ◽  
Genital Tract ◽  
Vaccine Development ◽  
Cd4 T Cell ◽  
Unique Challenge ◽  
Content Type ◽  
Chlamydia Muridarum ◽  
Genital Tract Infections ◽  
Tract Infections ◽  
Antigen Presenting

ABSTRACTUrogenitalChlamydiaserovars replicating in reproductive epithelium pose a unique challenge to host immunity and vaccine development. Previous studies have shown that CD4 T cells are necessary and sufficient to clear primaryChlamydia muridarumgenital tract infections in the mouse model, making a protective CD4 T cell response a logical endpoint for vaccine development. Our previous proteomics studies identified 13 candidateChlamydiaproteins for subunit vaccines. Of those, PmpG-1 is the most promising vaccine candidate. To further that work, we derived a PmpG303-311-specific multifunctional Th1 T cell clone, designated PmpG1.1, from an immune C57BL/6 mouse and used it to investigate the presentation of the PmpG303-311epitope by infected epithelial cells. Epithelial presentation of the PmpG303-311epitope required bacterial replication, occurred 15 to 18 h postinfection, and was unaffected by gamma interferon (IFN-γ) pretreatment. Unlike epitopes recognized by otherChlamydia-specific CD4 T cell clones, the PmpG303-311epitope persisted on splenic antigen-presenting cells (APC) of mice that cleared primary genital tract infections. PmpG1.1 was activated by unmanipulated irradiated splenocytes from immune mice without addition of exogenousChlamydiaantigen, and remarkably, activation of PmpG1.1 by unmanipulated immune splenocytes was stronger 6 months postinfection than it was 3 weeks postinfection. Enhanced presentation of PmpG303-311epitope on splenic APC 6 months postinfection reflects some type of “consolidation” of a protective immune response. Understanding the antigen-presenting cell populations responsible for presenting PmpG303-311early (3 weeks) and late (6 months) postinfection will likely provide important insights into stable protective immunity againstChlamydiainfections of the genital tract.

scholarly journals Mutational Analysis of the Chlamydia muridarum Plasticity Zone

2015 ◽  
Vol 83 (7) ◽  
pp. 2870-2881 ◽  
Author(s):  
Krithika Rajaram ◽  
Amanda M. Giebel ◽  
Evelyn Toh ◽  
Shuai Hu ◽  
Jasmine H. Newman ◽  
...  
Keyword(s):  
Cell Culture ◽  
Genital Tract ◽  
Mutational Analysis ◽  
Genomic Diversity ◽  
Infection Model ◽  
Plasticity Zone ◽  
Content Type ◽  
Chlamydia Muridarum ◽  
Ifn Γ ◽  
Tract Infections

Pathogenically diverseChlamydiaspp. can have surprisingly similar genomes.Chlamydia trachomatisisolates that cause trachoma, sexually transmitted genital tract infections (chlamydia), and invasive lymphogranuloma venereum (LGV) and the murine strainChlamydia muridarumshare 99% of their gene content. A region of high genomic diversity betweenChlamydiaspp. termed the plasticity zone (PZ) may encode niche-specific virulence determinants that dictate pathogenic diversity. We hypothesized that PZ genes might mediate the greater virulence and gamma interferon (IFN-γ) resistance ofC. muridarumcompared toC. trachomatisin the murine genital tract. To test this hypothesis, we isolated and characterized a series ofC. muridarumPZ nonsense mutants. Strains with nonsense mutations in chlamydial cytotoxins,guaBA-add, and a phospholipase D homolog developed normally in cell culture. Two of the cytotoxin mutants were less cytotoxic than the wild type, suggesting that the cytotoxins may be functional. However, none of the PZ nonsense mutants exhibited increased IFN-γ sensitivity in cell culture or were profoundly attenuated in a murine genital tract infection model. Our results suggest thatC. muridarumPZ genes are transcribed—and some may produce functional proteins—but are dispensable for infection of the murine genital tract.

scholarly journals The Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
Raina N. Fichorova ◽  
Pai-Lien Chen ◽  
Charles S. Morrison ◽  
Gustavo F. Doncel ◽  
Kevin Mendonca ◽  
...  
Keyword(s):  
Hiv Risk ◽  
Genital Tract ◽  
Molecular Mechanisms ◽  
Reproductive Age ◽  
Hormonal Contraceptives ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nugent Score ◽  
Content Type ◽  
Genital Tract Infections ◽  
Tract Infections

ABSTRACT Particular types of hormonal contraceptives (HCs) and genital tract infections have been independently associated with risk of HIV-1 acquisition. We examined whether immunity in women using injectable depot medroxyprogesterone acetate (DMPA), combined oral contraceptives (COC), or no HCs differs by the presence of cervicovaginal infections. Immune mediators were quantified in cervical swabs from 832 HIV-uninfected reproductive-age Ugandans and Zimbabweans. Bacterial infections and HIV were diagnosed by PCR, genital herpes serostatus by enzyme-linked immunosorbent assay (ELISA), altered microflora by Nugent score, and Trichomonas vaginalis and Candida albicans infection by wet mount. Generalized linear models utilizing Box-Cox-Power transformation examined associations between levels of mediators, infection status, and HCs. In no-HC users, T. vaginalis was associated with broadest spectrum of aberrant immunity (higher interleukin 1β [IL-1β], IL-8, macrophage inflammatory protein 3α [MIP-3α], β-defensin 2 [BD2], and IL-1 receptor antigen [IL-1RA]). In women with a normal Nugent score and no genital infection, compared to the no-HC group, COC users showed higher levels of IL-1β, IL-6, IL-8, and IL-1RA, while DMPA users showed higher levels of RANTES and lower levels of BD2, both associated with HIV seroconversion. These effects of COC were blunted in the presence of gonorrhea, chlamydia, trichomoniasis, candidiasis, and an abnormal Nugent score; however, RANTES was increased among COC users with herpes, chlamydia, and abnormal Nugent scores. The effect of DMPA was exacerbated by lower levels of IL-1RA in gonorrhea, chlamydia, or herpes, SLPI in gonorrhea, and IL-1β, MIP-3α, and IL-1RA/IL1β ratio in trichomoniasis. Thus, the effects of HC on cervical immunity depend on the genital tract microenvironment, and a weakened mucosal barrier against HIV may be a combined resultant of genital tract infections and HC use. IMPORTANCE In this article, we show that in young reproductive-age women most vulnerable to HIV, hormonal contraceptives are associated with altered cervical immunity in a manner dependent on the presence of genital tract infections. Through altered immunity, hormones may predispose women to bacterial and viral pathogens; conversely, a preexisting specific infection or disturbed vaginal microbiota may suppress the immune activation by levonorgestrel or exacerbate the suppressed immunity by DMPA, thus increasing HIV risk by their cumulative action. Clinical studies assessing the effects of contraception on HIV susceptibility and mucosal immunity may generate disparate results in populations that differ by microbiota background or prevalence of undiagnosed genital tract infections. A high prevalence of asymptomatic infections among HC users that remain undiagnosed and untreated raises even more concerns in light of their combined effects on biomarkers of HIV risk. The molecular mechanisms of the vaginal microbiome's simultaneous interactions with hormones and HIV remain to be elucidated.

scholarly journals Fur Represses Adhesion to, Invasion of, and Intracellular Bacterial Community Formation within Bladder Epithelial Cells and Motility in Uropathogenic Escherichia coli

2016 ◽  
Vol 84 (11) ◽  
pp. 3220-3231 ◽  
Author(s):  
Kumiko Kurabayashi ◽  
Tomohiro Agata ◽  
Hirofumi Asano ◽  
Haruyoshi Tomita ◽  
Hidetada Hirakawa
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Antimicrobial Agents ◽  
Host Cells ◽  
Type I ◽  
Wild Type ◽  
Content Type ◽  
Type I Fimbriae ◽  
Tract Infections

Uropathogenic Escherichia coli (UPEC) is a major pathogen that causes urinary tract infections (UTIs). This bacterium adheres to and invades the host cells in the bladder, where it forms biofilm-like polymicrobial structures termed intracellular bacterial communities (IBCs) that protect UPEC from antimicrobial agents and the host immune systems. Using genetic screening, we found that deletion of the fur gene, which encodes an iron-binding transcriptional repressor for iron uptake systems, elevated the expression of type I fimbriae and motility when UPEC was grown under iron-rich conditions, and it led to an increased number of UPEC cells adhering to and internalized in bladder epithelial cells. Consequently, the IBC colonies that the fur mutant formed in host cells were denser and larger than those formed by the wild-type parent strain. Fur is inactivated under iron-restricted conditions. When iron was depleted from the bacterial cultures, wild-type UPEC adhesion, invasion, and motility increased, similar to the case with the fur mutant. The purified Fur protein bound to regions upstream of fimA and flhD , which encode type I fimbriae and an activator of flagellar expression that contributes to motility, respectively. These results suggest that Fur is a repressor of fimA and flhD and that its repression is abolished under iron-depleted conditions. Based on our in vitro experiments, we conclude that UPEC adhesion, invasion, IBC formation, and motility are suppressed by Fur under iron-rich conditions but derepressed under iron-restricted conditions, such as in patients with UTIs.

scholarly journals Influence of Vaginal Bacteria and d- and l-Lactic Acid Isomers on Vaginal Extracellular Matrix Metalloproteinase Inducer: Implications for Protection against Upper Genital Tract Infections

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Steven S. Witkin ◽  
Helena Mendes-Soares ◽  
Iara M. Linhares ◽  
Aswathi Jayaram ◽  
William J. Ledger ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Lactic Acid ◽  
Matrix Metalloproteinase ◽  
Bacterial Communities ◽  
Relative Proportion ◽  
Extracellular Matrix Metalloproteinase Inducer ◽  
Content Type ◽  
Vaginal Secretions ◽  
Genital Tract Infections ◽  
Tract Infections

ABSTRACTWe evaluated levels of vaginal extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase (MMP-8) in vaginal secretions in relation to the composition of vaginal bacterial communities andd- andl-lactic acid levels. The composition of vaginal bacterial communities in 46 women was determined by pyrosequencing the V1 to V3 region of 16S rRNA genes. Lactobacilli were dominant in 71.3% of the women, followed byGardnerella(17.4%),Streptococcus(8.7%), andEnterococcus(2.2%). Of the lactobacillus-dominated communities, 51.5% were dominated byLactobacillus crispatus, 36.4% byLactobacillus iners, and 6.1% each byLactobacillus gasseriandLactobacillus jensenii. Concentrations ofl-lactic acid were slightly higher in lactobacillus-dominated vaginal samples, but most differences were not statistically significant.d-Lactic acid levels were higher in samples containingL. crispatusthan in those withL. iners(P< 0.0001) orGardnerella(P= 0.0002). The relative proportion ofd-lactic acid in vaginal communities dominated by species of lactobacilli was in concordance with the proportions found in axenic cultures of the various species grownin vitro. Levels ofl-lactic acid (P< 0.0001) and the ratio ofl-lactic acid tod-lactic acid (P= 0.0060), but not concentrations ofd-lactic acid, were also correlated with EMMPRIN concentrations. Moreover, vaginal concentrations of EMMPRIN and MMP-8 levels were highly correlated (P< 0.0001). Taken together, the data suggest the relative proportion ofl- tod-lactic acid isomers in the vagina may influence the extent of local EMMPRIN production and subsequent induction of MMP-8. The expression of these proteins may help determine the ability of bacteria to transverse the cervix and initiate upper genital tract infections.IMPORTANCEA large proportion of preterm births (>50%) result from infections caused by bacteria originating in the vagina, which requires that they traverse the cervix. Factors that influence susceptibility to these infections are not well understood; however, there is evidence that matrix metalloproteinase (MMP-8) is known to alter the integrity of the cervix. In this work, we show that concentrations of vaginal extracellular matrix metalloproteinase inducer (EMMPRIN) are influenced by members of the vaginal microbial community and concentrations ofd- orl-lactic acid isomers in vaginal secretions. Elevated levels ofd-lactic acid and the ratio ofd- tol-lactic acid influence EMMPRIN concentrations as well as MMP-8 levels. Thus, isomers of lactic acid may function as signaling molecules that alter host gene expression and influence risk of infection-related preterm birth.

scholarly journals Animal Models for Studying Female Genital Tract Infection with Chlamydia trachomatis

2013 ◽  
Vol 81 (9) ◽  
pp. 3060-3067 ◽  
Author(s):  
Evelien De Clercq ◽  
Isabelle Kalmar ◽  
Daisy Vanrompay
Keyword(s):  
Chlamydia Trachomatis ◽  
Animal Models ◽  
Genital Tract ◽  
Transmitted Disease ◽  
Female Genital Tract ◽  
Genital Tract Infection ◽  
Content Type ◽  
Genital Tract Infections ◽  
Tract Infections ◽  
Female Genital

ABSTRACTChlamydia trachomatisis a Gram-negative obligate intracellular bacterial pathogen. It is the leading cause of bacterial sexually transmitted disease in the world, with more than 100 million new cases of genital tract infections withC. trachomatisoccurring each year. Animal models are indispensable for the study ofC. trachomatisinfections and the development and evaluation of candidate vaccines. In this paper, the most commonly used animal models to study female genital tract infections withC. trachomatiswill be reviewed, namely, the mouse, guinea pig, and nonhuman primate models. Additionally, we will focus on the more recently developed pig model.

scholarly journals Ceramide and Toll-Like Receptor 4 Are Mobilized into Membrane Rafts in Response to Helicobacter pylori Infection in Gastric Epithelial Cells

2012 ◽  
Vol 80 (5) ◽  
pp. 1823-1833 ◽  
Author(s):  
Dah-Yuu Lu ◽  
Hui-Chen Chen ◽  
Mei-Shiang Yang ◽  
Yuan-Man Hsu ◽  
Hwai-Jeng Lin ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Lipid Rafts ◽  
Gastric Epithelial Cells ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Ags Cells ◽  
Content Type ◽  
Infected Cells ◽  
H Pylori

ABSTRACTHelicobacter pyloriinfection is thought to be involved in the development of several gastric diseases. TwoH. pylorivirulence factors (vacuolating cytotoxin A and cytotoxin-associated gene A) reportedly interact with lipid rafts in gastric epithelial cells. The role of Toll-like receptor (TLR)-mediated signaling in response toH. pyloriinfection has been investigated extensively in host cells. However, the receptor molecules in lipid rafts that are involved inH. pylori-induced innate sensing have not been well characterized. This study investigated whether lipid rafts play a role inH. pylori-induced ceramide secretion and TLR4 expression and thereby contribute to inflammation in gastric epithelial cells. We observed that both TLR4 and MD-2 mRNA and protein levels were significantly higher inH. pylori-infected AGS cells than in mock-infected cells. Moreover, significantly more TLR4 protein was detected in detergent-resistant membranes extracted fromH. pylori-infected AGS cells than in those extracted from mock-infected cells. However, this effect was attenuated by the treatment of cells with cholesterol-usurping agents, suggesting thatH. pylori-induced TLR4 signaling is dependent on cholesterol-rich microdomains. Similarly, the level of cellular ceramide was elevated and ceramide was translocated into lipid rafts afterH. pyloriinfection, leading to interleukin-8 (IL-8) production. Using the sphingomyelinase inhibitor imipramine, we observed thatH. pylori-induced TLR4 expression was ceramide dependent. These results indicate the mobilization of ceramide and TLR4 into lipid rafts byH. pyloriinfection in response to inflammation in gastric epithelial cells.

scholarly journals Persistent Mycoplasma genitalium Infection of Human Endocervical Epithelial Cells Elicits Chronic Inflammatory Cytokine Secretion

2012 ◽  
Vol 80 (11) ◽  
pp. 3842-3849 ◽  
Author(s):  
Chris L. McGowin ◽  
Rochelle S. Annan ◽  
Alison J. Quayle ◽  
Sheila J. Greene ◽  
Liang Ma ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Cytokine ◽  
Mycoplasma Genitalium ◽  
Clinical Findings ◽  
Cytokine Secretion ◽  
Host Cells ◽  
Content Type ◽  
Sexually Transmitted ◽  
Host Immune Responses ◽  
Tract Infections

ABSTRACTInfection withMycoplasma genitaliumhas been associated with male and female urogenital disease syndromes, including urethritis, cervicitis, pelvic inflammatory disease (PID), and tubal factor infertility. Basic investigations of mucosal cytotoxicity, microbial persistence, and host immune responses are imperative to understanding these inflammatory urogenital syndromes, particularly in females, considering the potential severity of upper tract infections. Here, we report thatM. genitaliumcan establish long-term infection of human endocervical epithelial cells that results in chronic inflammatory cytokine secretion and increased responsiveness to secondary Toll-like receptor (TLR) stimulation. Using a novel quantitative PCR assay,M. genitaliumwas shown to replicate from 0 to 80 days postinoculation (p.i.), during which at most time points the median ratio ofM. genitaliumorganisms to host cells was ≤10, indicating that low organism burdens are capable of eliciting chronic inflammation in endocervical epithelial cells. This observation is consistent with clinical findings in women. Persistently secreted cytokines predominately consisted of potent chemotactic and/or activating factors for phagocytes, including interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 1β (MIP-1β). Despite persistent cytokine elaboration, no host cell cytotoxicity was observed except with superphysiologic loads ofM. genitalium, suggesting that persistent infection occurs with minimal direct damage to the epithelium. However, it is hypothesized that chronic chemokine secretion with leukocyte trafficking to the epithelium could lead to significant inflammatory sequelae. Therefore, persistentM. genitaliuminfection could have important consequences for acquisition and/or pathogenesis of other sexually transmitted infections (STIs) and perhaps explain the positive associations between this organism and human immunodeficiency virus (HIV) shedding.

scholarly journals Macrolides Inhibit Fusobacterium nucleatum-Induced MUC5AC Production in Human Airway Epithelial Cells

2013 ◽  
Vol 57 (4) ◽  
pp. 1844-1849 ◽  
Author(s):  
Kentaro Nagaoka ◽  
Katsunori Yanagihara ◽  
Yosuke Harada ◽  
Koichi Yamada ◽  
Yohei Migiyama ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Respiratory Tract ◽  
Fusobacterium Nucleatum ◽  
Airway Epithelial Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Airway Epithelial ◽  
Content Type ◽  
Mucin Production ◽  
Tract Infections

ABSTRACTFusobacterium nucleatumis one of the most common anaerobic bacteria in periodontitis and is responsible for several extraoral infections, including respiratory tract diseases. In this study, we examined whetherF. nucleatuminduces mucin secretion in airway epithelial cells. We also examined the effects of macrolides onF. nucleatum-induced mucus production compared with the effects of other antibiotics that exert anti-anaerobic activities. The production of MUC5AC, the major core protein of mucin secreted from the airway surface epithelium, in bronchial epithelial cells after stimulation with culture supernatants (Sup) ofF. nucleatumwas analyzed by performing enzyme-linked immunosorbent assay and quantitative RT-PCR. The cell-signaling pathway ofF. nucleatumSup stimulation was also analyzed by Western blotting. For inhibition studies, cells were treated with azithromycin, clarithromycin, clindamycin (CLDM), and metronidazole (MTZ). TheF. nucleatumSup induced NCI-H292 cells to express MUC5AC at both the protein level and the mRNA level in both a time- and dose-dependent manner. Macrolides inhibitedF. nucleatumSup-induced MUC5AC production, while CLDM and MTZ were less effective.F. nucleatumSup induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and this induction was suppressed by macrolides.F. nucleatumSup-induced MUC5AC production was blocked by the ERK pathway inhibitor U0126.F. nucleatumis likely to contribute to excessive mucin production, which suggests that periodontitis may correlate with the pathogenesis of chronic respiratory tract infection. Macrolides seem to reduce this mucin production and might represent an additional means of therapeutic intervention forF. nucleatumrespiratory tract infections other than CLDM and MTZ.

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