scholarly journals Expression of Genes Encoding Innate Host Defense Molecules in Normal Human Monocytes in Response to Candida albicans

2005 ◽  
Vol 73 (6) ◽  
pp. 3714-3724 ◽  
Author(s):  
Hee Sup Kim ◽  
Eun Hwa Choi ◽  
Javed Khan ◽  
Emmanuel Roilides ◽  
Andrea Francesconi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Host Defense ◽  
Time Course ◽  
Transforming Growth Factor ◽  
Human Monocytes ◽  
Potent Inducer ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Normal Human ◽  
Defense Molecules

ABSTRACT Little is known about the regulation and coordinated expression of genes involved in the innate host response to Candida albicans. We therefore examined the kinetic profile of gene expression of innate host defense molecules in normal human monocytes infected with C. albicans using microarray technology. Freshly isolated peripheral blood monocytes from five healthy donors were incubated with C. albicans for 0 to 18 h in parallel with time-matched uninfected control cells. RNA from monocytes was extracted and amplified for microarray analysis, using a 42,421-gene cDNA chip. Expression of genes encoding proinflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 (IL-1), IL-6, and leukemia inhibitory factor, was markedly enhanced during the first 6 h and coincided with an increase in phagocytosis. Expression of these genes returned to near baseline by 18 h. Genes encoding chemokines, including IL-8; macrophage inflammatory proteins 1, 3, and 4; and monocyte chemoattractant protein 1, also were strongly up-regulated, with peak expression at 4 to 6 h, as were genes encoding chemokine receptors CCR1, CCR5, CCR7, and CXCR5. Expression of genes whose products may protect monocyte viability, such as BCL2-related protein, metallothioneins, CD71, and SOCS3, was up-regulated at 4 to 6 h and remained elevated throughout the 18-h time course. On the other hand, expression of genes encoding T-cell-regulatory molecules (e.g., IL-12, gamma interferon, and transforming growth factor β) was not significantly affected during the 18-h incubation. Moreover, genes encoding IL-15, the IL-13 receptor (IL-13Ra1), and CD14 were suppressed during the 18-h exposure to C. albicans. Thus, C. albicans is a potent inducer of a dynamic cascade of expression of genes whose products are related to the recruitment, activation, and protection of neutrophils and monocytes.

scholarly journals Mds3 Regulates Morphogenesis in Candida albicans through the TOR Pathway

2010 ◽  
Vol 30 (14) ◽  
pp. 3695-3710 ◽  
Author(s):  
Lucia F. Zacchi ◽  
Jonatan Gomez-Raja ◽  
Dana A. Davis
Keyword(s):  
Candida Albicans ◽  
Ribosomal Proteins ◽  
Ph Sensing ◽  
Tor Pathway ◽  
Preferential Expression ◽  
Human Fungal Pathogen ◽  
Expression Of Genes ◽  
Mucosal Surfaces ◽  
Genes Encoding ◽  
Morphological Defects

ABSTRACT The success of Candida albicans as a major human fungal pathogen is dependent on its ability to colonize and survive as a commensal on diverse mucosal surfaces. One trait required for survival and virulence in the host is the morphogenetic yeast-to-hypha transition. Mds3 was identified as a regulator of pH-dependent morphogenesis that functions in parallel with the classic Rim101 pH-sensing pathway. Microarray analyses revealed that mds3Δ/Δ cells had an expression profile indicative of a hyperactive TOR pathway, including the preferential expression of genes encoding ribosomal proteins and a decreased expression of genes involved in nitrogen source utilization. The transcriptional and morphological defects of the mds3Δ/Δ mutant were rescued by rapamycin, an inhibitor of TOR, and this rescue was lost in strains carrying the rapamycin-resistant TOR1-1 allele or an rbp1Δ/Δ deletion. Rapamycin also rescued the transcriptional and morphological defects associated with the loss of Sit4, a TOR pathway effector, but not the loss of Rim101 or Ras1. The sit4Δ/Δ and mds3Δ/Δ mutants had additional phenotypic similarities, suggesting that Sit4 and Mds3 function similarly in the TOR pathway. Finally, we found that Mds3 and Sit4 coimmunoprecipitate. Thus, Mds3 is a new member of the TOR pathway that contributes to morphogenesis in C. albicans as a regulator of this key morphogenetic pathway.

scholarly journals A time course transcriptomic analysis of host and injected oncogenic cells reveals new aspects of Drosophila immune defenses

2021 ◽  
Vol 118 (12) ◽  
pp. e2100825118
Author(s):  
Di Chen ◽  
Arghyashree Roychowdhury-Sinha ◽  
Pragya Prakash ◽  
Xiao Lan ◽  
Wenmin Fan ◽  
...  
Keyword(s):  
Time Course ◽  
Adult Males ◽  
Transcriptomic Response ◽  
Expression Of Genes ◽  
Regulated Expression ◽  
Genes Encoding ◽  
Lag Period ◽  
Induced Genes ◽  
As Stress ◽  
Kinetics Of

Oncogenic RasV12 cells [A. Simcox et al., PLoS Genet. 4, e1000142 (2008)] injected into adult males proliferated massively after a lag period of several days, and led to the demise of the flies after 2 to 3 wk. The injection induced an early massive transcriptomic response that, unexpectedly, included more than 100 genes encoding chemoreceptors of various families. The kinetics of induction and the identities of the induced genes differed markedly from the responses generated by injections of microbes. Subsequently, hundreds of genes were up-regulated, attesting to intense catabolic activities in the flies, active tracheogenesis, and cuticulogenesis, as well as stress and inflammation-type responses. At 11 d after the injections, GFP-positive oncogenic cells isolated from the host flies exhibited a markedly different transcriptomic profile from that of the host and distinct from that at the time of their injection, including in particular up-regulated expression of genes typical for cells engaged in the classical antimicrobial response of Drosophila.

Stomach regional specification requiresHoxa5-driven mesenchymal-epithelial signaling

Development ◽  
2002 ◽  
Vol 129 (17) ◽  
pp. 4075-4087 ◽  
Author(s):  
Josée Aubin ◽  
Ugo Déry ◽  
Margot Lemieux ◽  
Pierre Chailler ◽  
Lucie Jeannotte
Keyword(s):  
Growth Factor ◽  
Hox Genes ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Signaling Molecules ◽  
Loss Of Function ◽  
Expression Of Genes ◽  
Molecular Events ◽  
Genes Encoding ◽  
Fibroblast Growth Factor 10

The genetic control of gut regionalization relies on a hierarchy of molecular events in which the Hox gene family of transcription factors is suspected to be key participant. We have examined the role of Hox genes in gut patterning using the Hoxa5–/– mice as a model. Hoxa5 is expressed in a dynamic fashion in the mesenchymal component of the developing gut. Its loss of function results in gastric enzymatic anomalies in Hoxa5–/– surviving mutants that are due to perturbed cell specification during stomach development. Histological, biochemical and molecular characterization of the mutant stomach phenotype may be compatible with a homeotic transformation of the gastric mucosa. As the loss of mesenchymal Hoxa5 function leads to gastric epithelial defects, Hoxa5 should exert its action by controlling molecules involved in mesenchymal-epithelial signaling. Indeed, in the absence of Hoxa5 function, the expression of genes encoding for signaling molecules such as sonic hedgehog, Indian hedgehog, transforming growth factor β family members and fibroblast growth factor 10, is altered. These findings provide insight into the molecular controls of patterning events of the stomach, supporting the notion that Hoxa5 acts in regionalization and specification of the stomach by setting up the proper domains of expression of signaling molecules.

scholarly journals Global Transcriptional Response of Bacillus subtilis to Treatment with Subinhibitory Concentrations of Antibiotics That Inhibit Protein Synthesis

2005 ◽  
Vol 49 (5) ◽  
pp. 1915-1926 ◽  
Author(s):  
Janine T. Lin ◽  
Mariah Bindel Connelly ◽  
Chris Amolo ◽  
Suzie Otani ◽  
Debbie S. Yaver
Keyword(s):  
Protein Synthesis ◽  
Bacillus Subtilis ◽  
Time Course ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Global Gene Expression ◽  
Protein Synthesis Inhibitors ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Subinhibitory Concentrations

ABSTRACT Global gene expression patterns of Bacillus subtilis in response to subinhibitory concentrations of protein synthesis inhibitors (chloramphenicol, erythromycin, and gentamicin) were studied by DNA microarray analysis. B. subtilis cultures were treated with subinhibitory concentrations of protein synthesis inhibitors for 5, 15, 30, and 60 min, and transcriptional patterns were measured throughout the time course. Three major classes of genes were affected by the protein synthesis inhibitors: genes encoding transport/binding proteins, genes involved in protein synthesis, and genes involved in the metabolism of carbohydrates and related molecules. Similar expression patterns for a few classes of genes were observed due to treatment with chloramphenicol (0.4× MIC) or erythromycin (0.5× MIC), whereas expression patterns of gentamicin-treated cells were distinct. Expression of genes involved in metabolism of amino acids was altered by treatment with chloramphenicol and erythromycin but not by treatment with gentamicin. Heat shock genes were induced by gentamicin but repressed by chloramphenicol. Other genes induced by the protein synthesis inhibitors included the yheIH operon encoding ABC transporter-like proteins, with similarity to multidrug efflux proteins, and the ysbAB operon encoding homologs of LrgAB that function to inhibit cell wall cleavage (murein hydrolase activity) and convey penicillin tolerance in Staphylococcus aureus.

scholarly journals Release from Quorum-Sensing Molecules Triggers Hyphal Formation during Candida albicans Resumption of Growth

2005 ◽  
Vol 4 (7) ◽  
pp. 1203-1210 ◽  
Author(s):  
Brice Enjalbert ◽  
Malcolm Whiteway
Keyword(s):  
Candida Albicans ◽  
Quorum Sensing ◽  
Culture Medium ◽  
Pathogenic Fungus ◽  
Hyphal Growth ◽  
Growth Environment ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Hyphal Formation ◽  
Cyclin Genes

ABSTRACT Candida albicans is a pathogenic fungus able to change morphology in response to variations in its growth environment. Simple inoculation of stationary cells into fresh medium at 37°C, without any other manipulations, appears to be a powerful but transient inducer of hyphal formation; this process also plays a significant role in classical serum induction of hyphal formation. The mechanism appears to involve the release of hyphal repression caused by quorum-sensing molecules in the growth medium of stationary-phase cells, and farnesol has a strong but incomplete role in this process. We used DNA microarray technology to study both the resumption of growth of Candida albicans cells and molecular regulation involving farnesol. Maintaining farnesol in the culture medium during the resumption of growth both delays and reduces the induction of hypha-related genes yet triggers expression of genes encoding drug efflux components. The persistence of farnesol also prevents the repression of histone genes during hyphal growth and affects the expression of putative or demonstrated morphogenesis-regulating cyclin genes, such as HGC1, CLN3, and PCL2. The results suggest a model explaining the triggering of hyphae in the host based on quorum-sensing molecules.

scholarly journals Immunomodulatory Effects of Voriconazole on Monocytes Challenged with Aspergillus fumigatus: Differential Role of Toll-Like Receptors

2008 ◽  
Vol 52 (9) ◽  
pp. 3301-3306 ◽  
Author(s):  
Maria Simitsopoulou ◽  
Emmanuel Roilides ◽  
Fotini Paliogianni ◽  
Christodoulos Likartsis ◽  
John Ioannidis ◽  
...  
Keyword(s):  
Protein Expression ◽  
Aspergillus Fumigatus ◽  
Immunomodulatory Effect ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Protein Levels ◽  
Expression Of Genes ◽  
Tnf Α ◽  
Genes Encoding ◽  
Mrna And Protein Expression

ABSTRACT Voriconazole (VRC) has activity against Aspergillus fumigatus, the most frequent cause of invasive aspergillosis in immunocompromised patients. The combination of VRC and A. fumigatus hyphae induced a more pronounced profile of expression of genes encoding inflammatory molecules in human monocytes than Aspergillus alone did. Herein, we provide further evidence of the potential mechanism underlying this immunomodulatory effect of VRC on human monocytes in response to A. fumigatus hyphae. A significant additive antifungal effect was shown when VRC was combined with monocytes against A. fumigatus hyphae. Both A. fumigatus hyphae and VRC induced pronounced profiles of mRNA and protein expression of Toll-like receptor 2 (TLR2) as well as tumor necrosis factor alpha (TNF-α) in THP-1 monocytic cells compared to untreated cells. The VRC-induced increase was greater than that induced by hyphae. The combination of VRC and hyphae increased mRNA and protein expression of TLR2 and TNF-α to even higher levels than did either VRC or hyphae alone. In contrast, TLR4 expression, both at the mRNA and protein levels, was not increased by either VRC or hyphae or their combination. In addition, significantly more NF-κB was translocated to the nuclei of THP-1 cells treated with VRC than untreated cells. While VRC induced more NF-κB than hyphae did, treatment with the combination of the two factors induced the greatest NF-κB expression. The pronounced profile of TLR2 signaling, TNF-α expression, and NF-κB activation in the presence of VRC suggests an immunomodulatory effect leading to a more efficient response to A. fumigatus.

scholarly journals A Glucose Sensor in Candida albicans

2006 ◽  
Vol 5 (10) ◽  
pp. 1726-1737 ◽  
Author(s):  
Victoria Brown ◽  
Jessica A. Sexton ◽  
Mark Johnston
Keyword(s):  
Candida Albicans ◽  
Glucose Sensor ◽  
Glucose Sensing ◽  
Glucose Sensors ◽  
Glucose Levels ◽  
High Affinity ◽  
Expression Of Genes ◽  
Hexose Transporters ◽  
Genes Encoding ◽  
Sensor Glucose

ABSTRACT The Hgt4 protein of Candida albicans (orf19.5962) is orthologous to the Snf3 and Rgt2 glucose sensors of Saccharomyces cerevisiae that govern sugar acquisition by regulating the expression of genes encoding hexose transporters. We found that HGT4 is required for glucose induction of the expression of HGT12, HXT10, and HGT7, which encode apparent hexose transporters in C. albicans. An hgt4Δ mutant is defective for growth on fermentable sugars, which is consistent with the idea that Hgt4 is a sensor of glucose and similar sugars. Hgt4 appears to be sensitive to glucose levels similar to those in human serum (∼5 mM). HGT4 expression is repressed by high levels of glucose, which is consistent with the idea that it encodes a high-affinity sugar sensor. Glucose sensing through Hgt4 affects the yeast-to-hyphal morphological switch of C. albicans cells: hgt4Δ mutants are hypofilamented, and a constitutively signaling form of Hgt4 confers hyperfilamentation of cells. The hgt4Δ mutant is less virulent than wild-type cells in a mouse model of disseminated candidiasis. These results suggest that Hgt4 is a high-affinity glucose sensor that contributes to the virulence of C. albicans.

scholarly journals Heme Competition Triggers an Increase in the Pathogenic Potential of Porphyromonas gingivalis in Porphyromonas gingivalis-Candida albicans Mixed Biofilm

2020 ◽  
Vol 11 ◽  
Author(s):  
Yanyang Guo ◽  
Yu Wang ◽  
Yijin Wang ◽  
Yabing Jin ◽  
Chen Wang
Keyword(s):  
Candida Albicans ◽  
Porphyromonas Gingivalis ◽  
Morphological Changes ◽  
Single Species ◽  
Healthy Human ◽  
Pathogenic Potential ◽  
Expression Of Genes ◽  
Gene Level ◽  
Genes Encoding ◽  
Laser Confocal Microscope

As one of the main pathogens of periodontitis, Porphyromonas gingivalis often forms mixed biofilms with other bacteria or fungi under the gingiva, such as Candida albicans. Heme is an important iron source for P. gingivalis and C. albicans that supports their growth in the host. From the perspective of heme competition, this study aims to clarify that the competition for heme enhances the pathogenic potential of P. gingivalis during the interaction between P. gingivalis and C. albicans. Porphyromonas gingivalis single-species biofilm and P. gingivalis-C. albicans dual-species biofilm were established in a low- and high-heme environment. The results showed that the vitality of P. gingivalis was increased in the dual-species biofilm under the condition of low heme, and the same trend was observed under a laser confocal microscope. Furthermore, the morphological changes in P. gingivalis were observed by electron microscope, and the resistance of P. gingivalis in dual-species biofilm was stronger against the killing effect of healthy human serum and antibiotics. The ability of P. gingivalis to agglutinate erythrocyte was also enhanced in dual-species biofilm. These changes disappeared when heme was sufficient, which confirmed that heme competition was the cause of thepathogenicy change in P. gingivalis. Gene level analysis showed that P. gingivalis was in a superior position in the competition relationship by increasing the expression of heme utilization-related genes, such as HmuY, HmuR, HusA, and Tlr. In addition, the expression of genes encoding gingipains (Kgp, RgpA/B) was also significantly increased. They not only participate in the process of utilizing heme, but also are important components of the virulence factors of P. gingivalis. In conclusion, our results indicated that the pathogenic potential of P. gingivalis was enhanced by C. albicans through heme competition, which ultimately promoted the occurrence and development of periodontitis and, therefore, C. albicans subgingival colonization should be considered as a factor in assessing the risk of periodontitis.

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