scholarly journals Macrophage Polarization Alters Postphagocytosis Survivability of the CommensalStreptococcus gordonii

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Andrew J. Croft ◽  
Sarah Metcalfe ◽  
Kiyonobu Honma ◽  
Jason G. Kay
Keyword(s):  
Macrophage Polarization ◽  
Oral Bacteria ◽  
Ros Production ◽  
Systemic Diseases ◽  
Oxygen Species ◽  
Oral Streptococci ◽  
Phagocytic Cells ◽  
Content Type ◽  
Systemic Inflammatory Disease ◽  
Oral Streptococcus

ABSTRACTOral streptococci are generally considered commensal organisms; however, they are becoming recognized as important associate pathogens during the development of periodontal disease as well as being associated with several systemic diseases, including as a causative agent of infective endocarditis. An important virulence determinant of these bacteria is an ability to evade destruction by phagocytic cells, yet how this subversion occurs is mostly unknown. UsingStreptococcus gordoniias a model commensal oral streptococcus that is also associated with disease, we find that resistance to reactive oxygen species (ROS) with an active ability to damage phagosomes allows the bacterium to avoid destruction within macrophages. This ability to survive relies not only on the ROS resistance capabilities of the bacterium but also on ROS production by macrophages, with both being required for maximal survival of internalized bacteria. Importantly, we also show that this dependence on ROS production by macrophages for resistance has functional significance:S. gordoniiintracellular survival increases when macrophages are polarized toward an activated (M1) profile, which is known to result in prolonged phagosomal ROS production compared to that of alternatively (M2) polarized macrophages. We additionally find evidence of the bacterium being capable of both delaying the maturation of and damaging phagosomes. Taken together, these results provide essential insights regarding the mechanisms through which normally commensal oral bacteria can contribute to both local and systemic inflammatory disease.

scholarly journals Targeting the HUβ Protein PreventsPorphyromonas gingivalisfrom Entering into Preexisting Biofilms

2018 ◽  
Vol 200 (11) ◽  
pp. e00790-17 ◽  
Author(s):  
Christopher J. Rocco ◽  
Lauren O. Bakaletz ◽  
Steven D. Goodman
Keyword(s):  
Oral Cavity ◽  
Periodontal Disease ◽  
Porphyromonas Gingivalis ◽  
The United States ◽  
Extracellular Dna ◽  
Bacterial Biofilms ◽  
Oral Streptococci ◽  
Content Type ◽  
Oral Streptococcus ◽  
Streptococcal Species

ABSTRACTThe oral cavity is home to a wide variety of bacterial species, both commensal, such as various streptococcal species, and pathogenic, such asPorphyromonas gingivalis, one of the main etiological agents of periodontal disease. Our understanding of how these bacteria ultimately cause disease is highly dependent upon understanding how they coexist and interact with one another in biofilm communities and the mechanisms by which biofilms are formed. Our research has demonstrated that the DNABII family of DNA-binding proteins are important components of the extracellular DNA (eDNA)-dependent matrix of bacterial biofilms and that sequestering these proteins via protein-specific antibodies results in the collapse of the biofilm structure and release of the resident bacteria. While the high degree of similarity among the DNABII family of proteins has allowed antibodies derived against specific DNABII proteins to disrupt biofilms formed by a wide range of bacterial pathogens, the DNABII proteins ofP. gingivalishave proven to be antigenically distinct, allowing us to determine if we can use anti-P. gingivalisHUβ antibodies to specifically target this species for removal from a mixed-species biofilm. Importantly, despite forming homotypic biofilmsin vitro,P. gingivalismust enter preexisting biofilmsin vivoin order to persist within the oral cavity. The data presented here indicate that antibodies derived against theP. gingivalisDNABII protein, HUβ, reduce by half the amount ofP. gingivalisorganisms entering into preexisting biofilm formed by four oral streptococcal species. These results support our efforts to develop methods for preventing and treating periodontal disease.IMPORTANCEPeriodontitis is one of the most prevalent chronic infections, affecting 40 to 50% of the population of the United States. The root cause of periodontitis is the presence of bacterial biofilms within the gingival space, withPorphyromonas gingivalisbeing strongly associated with the development of the disease. Periodontitis also increases the risk of secondary conditions and infections such as atherosclerosis and infective endocarditis caused by oral streptococci. To induce periodontitis,P. gingivalisneeds to incorporate into preformed biofilms, with oral streptococci being important binding partners. Our research demonstrates that targeting DNABII proteins with an antibody disperses oral streptococcus biofilm and preventsP. gingivalisentry into oral streptococcus biofilm. These results suggest potential therapeutic treatments for endocarditis caused by streptococci as well as periodontitis.

scholarly journals Genetic Analysis of Mutacin B-Ny266, a Lantibiotic Active against Caries Pathogens

2020 ◽  
Vol 202 (12) ◽  
Author(s):  
Delphine Dufour ◽  
Abdelahhad Barbour ◽  
Yuki Chan ◽  
Marcus Cheng ◽  
Taimoor Rahman ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Dental Plaque ◽  
Oral Bacteria ◽  
Oral Streptococci ◽  
Chromosomal Locus ◽  
Content Type ◽  
Genes Encoding ◽  
Plaque Biofilm

ABSTRACT Bacteriocins are ribosomally synthesized proteinaceous antibacterial peptides. They selectively interfere with the growth of other bacteria. The production and secretion of bacteriocins confer a distinct ecological advantage to the producer in competing against other bacteria that are present in the same ecological niche. Streptococcus mutans, a significant contributor to the development of dental caries, is one of the most prolific producers of bacteriocins, known as mutacins in S. mutans. In this study, we characterized the locus encoding mutacin B-Ny266, a lantibiotic with a broad spectrum of activity. The chromosomal locus is composed of six predicted operon structures encoding proteins involved in regulation, antimicrobial activity, biosynthesis, modification, transport, and immunity. Mutacin B-Ny266 was purified from semisolid cultures, and two inhibitory peptides, LanA and LanA′, were detected. Both peptides were highly modified. Such modifications include dehydration of serine and threonine and the formation of a C-terminal aminovinyl-cysteine (AviCys) ring. While LanA peptide alone is absolutely required for antimicrobial activity, the presence of LanA′ enhanced the activity of LanA, suggesting that B-Ny266 may function as a two-peptide lantibiotic. The activation of lanAA′ expression is most likely controlled by the conserved two-component system NsrRS, which is activated by LanA peptide but not by LanA′. The chromosomal locus encoding mutacin B-Ny266 was not universally conserved in all sequenced S. mutans genomes. Intriguingly, the genes encoding LanAA′ peptides were restricted to the most invasive serotypes of S. mutans. IMPORTANCE Although dental caries is largely preventable, it remains the most common and costly infectious disease worldwide. Caries is initiated by the presence of dental plaque biofilm that contains Streptococcus mutans, a species extensively characterized by its role in caries development and formation. S. mutans deploys an arsenal of strategies to establish itself within the oral cavity. One of them is the production of bacteriocins that confer a competitive advantage by targeting and killing closely related competitors. In this work, we found that mutacin B-Ny266 is a potent lantibiotic that is effective at killing a wide array of oral streptococci, including nearly all S. mutans strains tested. Lantibiotics produced by oral bacteria could represent a promising strategy to target caries pathogens embedded in dental plaque biofilm.

scholarly journals Modulation of Neutrophil Extracellular Trap and Reactive Oxygen Species Release by Periodontal Bacteria

2017 ◽  
Vol 85 (12) ◽  
Author(s):  
Josefine Hirschfeld ◽  
Phillipa C. White ◽  
Michael R. Milward ◽  
Paul R. Cooper ◽  
Iain L. C. Chapple
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Reactive Oxygen ◽  
Oral Bacteria ◽  
Oxygen Species ◽  
Antimicrobial Proteins ◽  
Bacterial Killing ◽  
Content Type ◽  
Periodontal Bacteria ◽  
Net Release

ABSTRACT Oral bacteria are the main trigger for the development of periodontitis, and some species are known to modulate neutrophil function. This study aimed to explore the release of neutrophil extracellular traps (NETs), associated antimicrobial proteins, and reactive oxygen species (ROS) in response to periodontal bacteria, as well as the underlying pathways. Isolated peripheral blood neutrophils were stimulated with 19 periodontal bacteria. NET and ROS release, as well as the expression of NET-bound antimicrobial proteins, elastase, myeloperoxidase, and cathepsin G, in response to these species was measured using fluorescence-based assays. NET and ROS release was monitored after the addition of NADP (NADPH) oxidase pathway modulators and inhibitors of Toll-like receptors (TLRs). Moreover, bacterial entrapment by NETs was visualized microscopically, and bacterial killing was assessed by bacterial culture. Certain microorganisms, e.g., Veillonella parvula and Streptococcus gordonii, stimulated higher levels of ROS and NET release than others. NETs were found to entrap, but not kill, all periodontal bacteria tested. NADPH oxidase pathway modulators decreased ROS production but not NET production in response to the bacteria. Interestingly, TLR inhibitors did not impact ROS and NET release. These data suggest that the variability in the neutrophil response toward different bacteria may contribute to the pathogenesis of periodontal diseases by mechanisms such as bacterial avoidance of host responses and activation of neutrophils. Moreover, our results indicate that bacterium-stimulated NET release may arise in part via NADPH oxidase-independent mechanisms. The role of TLR signaling in bacterium-induced ROS and NET release needs to be further elucidated.

scholarly journals PerR-Regulated Manganese Ion Uptake Contributes to Oxidative Stress Defense in an Oral Streptococcus

2014 ◽  
Vol 80 (8) ◽  
pp. 2351-2359 ◽  
Author(s):  
Xinhui Wang ◽  
Huichun Tong ◽  
Xiuzhu Dong
Keyword(s):  
Iron Homeostasis ◽  
Critical Role ◽  
Brain Heart Infusion ◽  
Oral Streptococci ◽  
Content Type ◽  
Manganese Ion ◽  
Gram Positive Bacteria ◽  
Wild Type Phenotype ◽  
Oral Streptococcus ◽  
Antioxidative Stress

ABSTRACTMetal homeostasis plays a critical role in antioxidative stress.Streptococcus oligofermentans, an oral commensal facultative anaerobe lacking catalase activity, produces and tolerates abundant H2O2, whereas Dpr (an Fe2+-chelating protein)-dependent H2O2protection does not confer such high tolerance. Here, we report that inactivation ofperR, a peroxide-responsive repressor that regulates zinc and iron homeostasis in Gram-positive bacteria, increased the survival of H2O2-pulsedS. oligofermentans32-fold and elevated cellular manganese 4.5-fold.perRcomplementation recovered the wild-type phenotype. When grown in 0.1 to 0.25 mM MnCl2,S. oligofermentansincreased survival after H2O2stress 2.5- to 23-fold, and even greater survival was found for theperRmutant, indicating that PerR is involved in Mn2+-mediated H2O2resistance inS. oligofermentans. Mutation ofmntAcould not be obtained in brain heart infusion (BHI) broth (containing ∼0.4 μM Mn2+) unless it was supplemented with ≥2.5 μM MnCl2and caused 82 to 95% reduction of the cellular Mn2+level, whilemntABCoverexpression increased cellular Mn2+2.1- to 4.5-fold. Thus, MntABC was identified as a high-affinity Mn2+transporter inS. oligofermentans. mntAmutation reduced the survival of H2O2-pulsedS. oligofermentans5.7-fold, whilemntABCoverexpression enhanced H2O2-challenged survival 12-fold, indicating that MntABC-mediated Mn2+uptake is pivotal to antioxidative stress inS. oligofermentans. perRmutation or H2O2pulsing upregulatedmntABC, while H2O2-induced upregulation diminished in theperRmutant. This suggests thatperRrepressesmntABCexpression but H2O2can release the suppression. In conclusion, this work demonstrates that PerR regulates manganese homeostasis inS. oligofermentans, which is critical to H2O2stress defenses and may be distributed across all oral streptococci lacking catalase.

scholarly journals Induction of Mitochondrial Reactive Oxygen Species Production by Itraconazole, Terbinafine, and Amphotericin B as a Mode of Action against Aspergillus fumigatus

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Elena Shekhova ◽  
Olaf Kniemeyer ◽  
Axel A. Brakhage
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Peroxidation ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Complex I ◽  
Reactive Oxygen ◽  
Antifungal Compounds ◽  
Ros Production ◽  
Oxygen Species ◽  
Content Type

ABSTRACT Drug resistance in fungal pathogens is of incredible importance to global health, yet the mechanisms of drug action remain only loosely defined. Antifungal compounds have been shown to trigger the intracellular accumulation of reactive oxygen species (ROS) in human-pathogenic yeasts, but the source of those ROS remained unknown. In the present study, we examined the role of endogenous ROS for the antifungal activity of the three different antifungal substances itraconazole, terbinafine, and amphotericin B, which all target the fungal cell membrane. All three antifungals had an impact on fungal redox homeostasis by causing increased intracellular ROS production. Interestingly, the elevated ROS levels induced by antifungals were abolished by inhibition of the mitochondrial respiratory complex I with rotenone. Further, evaluation of lipid peroxidation using the thiobarbituric acid assay revealed that rotenone pretreatment decreased ROS-induced lipid peroxidation during incubation of Aspergillus fumigatus with itraconazole and terbinafine. By applying the mitochondrion-specific lipid peroxidation probe MitoPerOx, we also confirmed that ROS are induced in mitochondria and subsequently cause significant oxidation of mitochondrial membrane in the presence of terbinafine and amphotericin B. To summarize, our study suggests that the induction of ROS production contributes to the ability of antifungal compounds to inhibit fungal growth. Moreover, mitochondrial complex I is the main source of deleterious ROS production in A. fumigatus challenged with antifungal compounds.

scholarly journals CD157 Confers Host Resistance to Mycobacterium tuberculosis via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Qianting Yang ◽  
Mingfeng Liao ◽  
Wenfei Wang ◽  
Mingxia Zhang ◽  
Qi Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mycobacterium Tuberculosis ◽  
Host Resistance ◽  
Ros Production ◽  
Oxygen Species ◽  
Effective Strategy ◽  
Content Type ◽  
Protein Levels

ABSTRACT Recruitment of monocytes to the infection site is critical for host resistance against Mycobacterium tuberculosis. CD157 has a crucial role in neutrophil and monocyte transendothelial migration and adhesion, but its role in tuberculosis (TB) is unclear. Here, we show that both mRNA and protein levels of Cd157 are significantly increased during M. tuberculosis infection. Deficiency of Cd157 impaired host response to M. tuberculosis infection by increasing bacterial burden and inflammation in the lung in the murine TB model. In vitro experiments show that the bactericidal ability was compromised in Cd157 knockout (KO) macrophages, which was due to impaired M. tuberculosis-induced reactive oxygen species (ROS) production. We further reveal that CD157 interacts with TLR2 and PKCzeta and facilitates M. tuberculosis-induced ROS production in Cd157 KO macrophages, which resulted in enhanced M. tuberculosis killing. For the clinic aspect, we observe that the expression of CD157 decreases after effective anti-TB chemotherapy. CD157 is specifically increased in pleural fluid in tuberculous pleurisy patients compared to pneumonia and lung cancer patients. Interestingly, the levels of soluble CD157 (sCD157) correlate with human peripheral monocyte-derived macrophage bactericidal activity. Exogenous application of sCD157 could compensate for macrophage bactericidal ability and restore ROS production. In conclusion, we have identified a novel protective immune function of CD157 during M. tuberculosis infection via TLR2-dependent ROS production. Application of sCD157 might be an effective strategy for host-directed therapy against TB in those with insufficient CD157 production. IMPORTANCE Tuberculosis, a chronic bacterial disease caused by Mycobacterium tuberculosis, remains a major global health problem. CD157, a dual-function receptor and β-NAD+-metabolizing ectoenzyme, promotes cell polarization, regulates chemotaxis induced through the high-affinity fMLP receptor, and controls transendothelial migration. The role of CD157 in TB pathogenesis remains unknown. In this study, we find that both mRNA and protein levels of CD157 are significantly increased in TB. Deficiency of CD157 impaired host defense against M. tuberculosis infection both in vivo and in vitro, which is mediated by an interaction among CD157, TLR2, and PKCzeta. This interaction facilitates M. tuberculosis-induced macrophagic ROS production, which enhances macrophage bactericidal activity. Interestingly, the sCD157 level in plasma is reversibly associated with MDM M. tuberculosis killing activity. By uncovering the role of CD157 in pathogenesis of TB for the first time, our work demonstrated that application of soluble CD157 might be an effective strategy for host-directed therapy against TB.

scholarly journals Characterization of the Streptococcus mutans SMU.1703c-SMU.1702c Operon Reveals Its Role in Riboflavin Import and Response to Acid Stress

2020 ◽  
Vol 203 (2) ◽  
pp. e00293-20
Author(s):  
Matthew E. Turner ◽  
Khanh Huynh ◽  
Ronan K. Carroll ◽  
Sang-Joon Ahn ◽  
Kelly C. Rice
Keyword(s):  
Oral Cavity ◽  
Streptococcus Mutans ◽  
Tooth Enamel ◽  
Acid Stress ◽  
Oral Bacteria ◽  
Flavin Mononucleotide ◽  
Dependent Manner ◽  
Oral Streptococci ◽  
Uncharacterized Protein ◽  
Content Type

ABSTRACTStreptococcus mutans utilizes numerous metabolite transporters to obtain essential nutrients in the “feast or famine” environment of the human mouth. S. mutans and most other streptococci are considered auxotrophic for several essential vitamins including riboflavin (vitamin B2), which is used to generate key cofactors and to perform numerous cellular redox reactions. Despite the well-known contributions of this vitamin to central metabolism, little is known about how S. mutans obtains and metabolizes B2. The uncharacterized protein SMU.1703c displays high sequence homology to the riboflavin transporter RibU. Deletion of SMU.1703c hindered S. mutans growth in complex and defined medium in the absence of saturating levels of exogenous riboflavin, whereas deletion of cotranscribed SMU.1702c alone had no apparent effect on growth. Expression of SMU.1703c in a Bacillus subtilis riboflavin auxotroph functionally complemented growth in nonsaturating riboflavin conditions. S. mutans was also able to grow on flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN) in an SMU.1703c-dependent manner. Deletion of SMU.1703c and/or SMU.1702c impacted S. mutans acid stress tolerance, as all mutants showed improved growth at pH 5.5 compared to that of the wild type when medium was supplemented with saturating riboflavin. Cooccurrence of SMU.1703c and SMU.1702c, a hypothetical PAP2 family acid phosphatase gene, appears unique to the streptococci and may suggest a connection of SMU.1702c to the acquisition or metabolism of flavins within this genus. Identification of SMU.1703c as a RibU-like riboflavin transporter furthers our understanding of how S. mutans acquires essential micronutrients within the oral cavity and how this pathogen successfully competes within nutrient-starved oral biofilms.IMPORTANCE Dental caries form when acid produced by oral bacteria erodes tooth enamel. This process is driven by the fermentative metabolism of cariogenic bacteria, most notably Streptococcus mutans. Nutrient acquisition is key in the competitive oral cavity, and many organisms have evolved various strategies to procure carbon sources or necessary biomolecules. B vitamins, such as riboflavin, which many oral streptococci must scavenge from the oral environment, are necessary for survival within the competitive oral cavity. However, the primary mechanism and proteins involved in this process remain uncharacterized. This study is important because it identifies a key step in S. mutans riboflavin acquisition and cofactor generation, which may enable the development of novel anticaries treatment strategies via selective targeting of metabolite transporters.

scholarly journals A New Pneumococcal Capsule Type, 10D, is the 100th Serotype and Has a Large cps Fragment from an Oral Streptococcus

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Feroze Ganaie ◽  
Jamil S. Saad ◽  
Lesley McGee ◽  
Andries J. van Tonder ◽  
Stephen D. Bentley ◽  
...  
Keyword(s):  
Chemical Structure ◽  
Capsular Polysaccharides ◽  
Oral Streptococci ◽  
Genetic Studies ◽  
Content Type ◽  
Capsule Type ◽  
Oral Streptococcus ◽  
Interspecies Recombination ◽  
Large Repertoire ◽  
Unique Chemical

ABSTRACT Streptococcus pneumoniae (pneumococcus) is a major human pathogen producing structurally diverse capsular polysaccharides. Widespread use of highly successful pneumococcal conjugate vaccines (PCVs) targeting pneumococcal capsules has greatly reduced infections by the vaccine types but increased infections by nonvaccine serotypes. Herein, we report a new and the 100th capsule type, named serotype 10D, by determining its unique chemical structure and biosynthetic roles of all capsule synthesis locus (cps) genes. The name 10D reflects its serologic cross-reaction with serotype 10A and appearance of cross-opsonic antibodies in response to immunization with 10A polysaccharide in a 23-valent pneumococcal vaccine. Genetic analysis showed that 10D cps has three large regions syntenic to and highly homologous with cps loci from serotype 6C, serotype 39, and an oral streptococcus strain (S. mitis SK145). The 10D cps region syntenic to SK145 is about 6 kb and has a short gene fragment of wciNα at the 5′ end. The presence of this nonfunctional wciNα fragment provides compelling evidence for a recent interspecies genetic transfer from oral streptococcus to pneumococcus. Since oral streptococci have a large repertoire of cps loci, widespread PCV usage could facilitate the appearance of novel serotypes through interspecies recombination. IMPORTANCE The polysaccharide capsule is essential for the pathogenicity of pneumococcus, which is responsible for millions of deaths worldwide each year. Currently available pneumococcal vaccines are designed to elicit antibodies to the capsule polysaccharides of the pneumococcal isolates commonly causing diseases, and the antibodies provide protection only against the pneumococcus expressing the vaccine-targeted capsules. Since pneumococci can produce different capsule polysaccharides and therefore reduce vaccine effectiveness, it is important to track the appearance of novel pneumococcal capsule types and how these new capsules are created. Herein, we describe a new and the 100th pneumococcal capsule type with unique chemical and serological properties. The capsule type was named 10D for its serologic similarity to 10A. Genetic studies provide strong evidence that pneumococcus created 10D capsule polysaccharide by capturing a large genetic fragment from an oral streptococcus. Such interspecies genetic exchanges could greatly increase diversity of pneumococcal capsules and complicate serotype shifts.

scholarly journals Functional Analysis of theTrichoderma harzianum nox1Gene, Encoding an NADPH Oxidase, Relates Production of Reactive Oxygen Species to Specific Biocontrol Activity against Pythium ultimum

2011 ◽  
Vol 77 (9) ◽  
pp. 3009-3016 ◽  
Author(s):  
M. Montero-Barrientos ◽  
R. Hermosa ◽  
R. E. Cardoza ◽  
S. Gutiérrez ◽  
E. Monte
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Pythium Ultimum ◽  
Eukaryotic Cells ◽  
Ros Production ◽  
Oxygen Species ◽  
Wild Type ◽  
Nadph Oxidases ◽  
Content Type ◽  
Biocontrol Activity

ABSTRACTThe synthesis of reactive oxygen species (ROS) is one of the first events following pathogenic interactions in eukaryotic cells, and NADPH oxidases are involved in the formation of such ROS. Thenox1gene ofTrichoderma harzianumwas cloned, and its role in antagonism against phytopathogens was analyzed innox1-overexpressed transformants. The increased levels ofnox1expression in these transformants were accompanied by an increase in ROS production during their direct confrontation withPythium ultimum. The transformants displayed an increased hydrolytic pattern, as determined by comparing protease, cellulase, and chitinase activities with those for the wild type. In confrontation assays againstP. ultimumthenox1-overexpressed transformants were more effective than the wild type, but not in assays againstBotrytis cinereaorRhizoctonia solani. A transcriptomic analysis using aTrichodermahigh-density oligonucleotide (HDO) microarray also showed that, compared to gene expression for the interaction of wild-typeT. harzianumandP. ultimum, genes related to protease, cellulase, and chitinase activities were differentially upregulated in the interaction of anox1-overexpressed transformant with this pathogen. Our results show thatnox1is involved inT. harzianumROS production and antagonism againstP. ultimum.

scholarly journals The Aryl Hydrocarbon Receptor Modulates Production of Cytokines and Reactive Oxygen Species and Development of Myocarditis during Trypanosoma cruzi Infection

2016 ◽  
Vol 84 (10) ◽  
pp. 3071-3082 ◽  
Author(s):  
Andréia Barroso ◽  
Melisa Gualdrón-López ◽  
Lísia Esper ◽  
Fátima Brant ◽  
Ronan R. S. Araújo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Trypanosoma Cruzi ◽  
Aryl Hydrocarbon Receptor ◽  
Reactive Oxygen ◽  
T Cell Subsets ◽  
Cytokine Signaling ◽  
Ros Production ◽  
Oxygen Species ◽  
Content Type ◽  
Aryl Hydrocarbon

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in controlling several aspects of immune responses, including the activation and differentiation of specific T cell subsets and antigen-presenting cells, thought to be relevant in the context of experimentalTrypanosoma cruziinfection. The relevance of AhR for the outcome ofT. cruziinfection is not known and was investigated here. We infected wild-type (WT) mice and AhR knockout (AhR KO) mice withT. cruzi(Y strain) and determined levels of parasitemia, myocardial inflammation and fibrosis, expression of AhR/cytokines/suppressor of cytokine signaling (SOCS) (spleen/heart), and production of nitric oxide (NO), reactive oxygen species (ROS), and peroxynitrite (ONOO−) (spleen). AhR expression was increased in the heart of infected WT mice. Infected AhR KO mice displayed significantly reduced parasitemia, inflammation, and fibrosis of the myocardium. This was associated with an anticipated increased immune response characterized by increased levels of inflammatory cytokines and reduced expression of SOCS2 and SOCS3 in the heart.In vitro, AhR deficiency caused impairment in parasite replication and decreased levels of ROS production. In conclusion, AhR influences the development of murine Chagas disease by modulating ROS production and regulating the expression of key physiological regulators of inflammation, SOCS1 to -3, associated with the production of cytokines during experimentalT. cruziinfection.

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