scholarly journals Keratinocyte Expression of Human β Defensin 2 following Bacterial Infection: Role in Cutaneous Host Defense

2003 ◽  
Vol 10 (1) ◽  
pp. 161-166 ◽  
Author(s):  
James G. H. Dinulos ◽  
Laurel Mentele ◽  
L. Page Fredericks ◽  
Beverly A. Dale ◽  
Gary L. Darmstadt
Keyword(s):  
Host Defense ◽  
Staphylococcus Epidermidis ◽  
Pathogenic Bacteria ◽  
Skin Surface ◽  
Immune Defense ◽  
Skin Infections ◽  
Reverse Transcription Pcr ◽  
Relative Tolerance ◽  
Disease Induction ◽  
Stimulation Of

ABSTRACT Human β defensin 2 (hβD-2) is thought to play an important role in cutaneous immune defense. We hypothesized that (i) keratinocyte expression of hβD-2, measured by reverse transcription-PCR, would be upregulated in response to challenge with pathogenic bacteria, particularly highly adherent strains of Streptococcus pyogenes and Staphylococcus aureus, and (ii) hβD-2 would have potent antimicrobial activity against pathogenic but not commensal organisms. Expression of hβD-2 was induced consistently by S. aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa, whereas strains of S. pyogenes were poor and variable inducers of hβD-2. No correlation was found between levels of bacterial adherence and keratinocyte expression of hβD-2. S. pyogenes was significantly more sensitive to killing by hβD-2 than S. epidermidis. We conclude that the ability to induce hβD-2 expression in combination with sensitivity to its antimicrobial effects may contribute to the rarity of skin infections with the gram-negative bacterial organisms, whereas lack of stimulation of hβD-2 expression by S. pyogenes may be important in its ability to evade innate defenses and cause skin disease. Induction of expression of hβD-2 but relative tolerance to it may enable S. epidermidis to survive on the skin surface and modulate hβD-2 expression when the stratum corneum barrier is disrupted.

scholarly journals AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nathaniel B. Bone ◽  
Eugene J. Becker ◽  
Maroof Husain ◽  
Shaoning Jiang ◽  
Anna A. Zmijewska ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Inflammatory Responses ◽  
Abdominal Sepsis ◽  
Immune Defense ◽  
Bacterial Killing ◽  
Lung Infections ◽  
Sepsis Survivors ◽  
The Impact

AbstractMetabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2−/− murine macrophages. In vivo, the impact of AMPK and Parkin was determined in mice subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. Mice were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient mice/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.

Differential Oxidative Modulation of Voltage-Dependent K+ Currents in Rat Hippocampal Neurons

2002 ◽  
Vol 87 (6) ◽  
pp. 2990-2995 ◽  
Author(s):  
Wolfgang Müller ◽  
Katrin Bittner
Keyword(s):  
Hydrogen Peroxide ◽  
Hippocampal Neurons ◽  
Immune Defense ◽  
Delayed Rectifier ◽  
Delayed Rectifier Current ◽  
Cell Recording ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
K Currents ◽  
Stimulation Of

Oxidative stress is enhanced by [Ca2+]i-dependent stimulation of phospholipases and mitochondria and has been implicated in immune defense, ischemia, and excitotoxicity. Using whole cell recording from hippocampal neurons, we show that arachidonic acid (AA) and hydrogen peroxide (H2O2) both reduce the transient K+ current I A by −54 and −68%, respectively, and shift steady-state inactivation by −10 and −15 mV, respectively. While AA was effective at an extracellular concentration of 1 μM and an intracellular concentration of 1 pM, extracellular H2O2 was equally effective only at a concentration >800 μM (0.0027%). In contrast to AA, H2O2 decreased the slope of activation and increased the slope of inactivation of I A and reduced the sustained delayed rectifier current I K(V) by 22% and shifted its activation by −9 mV. Intracellular application of the antioxidant glutathione (GSH, 2–5 mM) blocked all effects of AA and the reduction of I A by H2O2. In contrast, intracellular GSH enhanced reduction of I K(V) by H2O2. Decrease of the slope of activation and increase of the slope of inactivation of I A by hydrogen peroxide was blocked and reversed to a decrease, respectively, by intracellular application of GSH. Intracellular GSH did not prevent H2O2 to shift inactivation and activation of I A and activation of I K(V) to more negative potentials. We conclude, that AA and H2O2modulate voltage-activated K currents differentially by oxidation of GSH accessible intracellular and GSH inaccessible extracellular K+-channel domains, thereby presumably affecting neuronal information processing and oxidative damage.

scholarly journals Identification of Genes Encoding Antimicrobial Proteins in Langerhans Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Aislyn Oulee ◽  
Feiyang Ma ◽  
Rosane M. B. Teles ◽  
Bruno J. de Andrade Silva ◽  
Matteo Pellegrini ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Host Defense ◽  
Langerhans Cells ◽  
Scientific Literature ◽  
Inflammatory Responses ◽  
Microbial Pathogens ◽  
Anatomical Location ◽  
Skin Infections ◽  
Antimicrobial Proteins ◽  
Genes Encoding

Langerhans cells (LCs) reside in the epidermis where they are poised to mount an antimicrobial response against microbial pathogens invading from the outside environment. To elucidate potential pathways by which LCs contribute to host defense, we mined published LC transcriptomes deposited in GEO and the scientific literature for genes that participate in antimicrobial responses. Overall, we identified 31 genes in LCs that encode proteins that contribute to antimicrobial activity, ten of which were cross-validated in at least two separate experiments. Seven of these ten antimicrobial genes encode chemokines, CCL1, CCL17, CCL19, CCL2, CCL22, CXCL14 and CXCL2, which mediate both antimicrobial and inflammatory responses. Of these, CCL22 was detected in seven of nine transcriptomes and by PCR in cultured LCs. Overall, the antimicrobial genes identified in LCs encode proteins with broad antibacterial activity, including against Staphylococcus aureus, which is the leading cause of skin infections. Thus, this study illustrates that LCs, consistent with their anatomical location, are programmed to mount an antimicrobial response against invading pathogens in skin.

scholarly journals Combined Stimulation of Toll-Like Receptor 5 and NOD1 Strongly Potentiates Activity of NF-κB, Resulting in Enhanced Innate Immune Reactions and Resistance to Salmonella enterica Serovar Typhimurium Infection

2013 ◽  
Vol 81 (10) ◽  
pp. 3855-3864 ◽  
Author(s):  
Amir I. Tukhvatulin ◽  
Ilya I. Gitlin ◽  
Dmitry V. Shcheblyakov ◽  
Natalia M. Artemicheva ◽  
Lyudmila G. Burdelya ◽  
...  
Keyword(s):  
Critical Role ◽  
Immune Defense ◽  
Innate Immune ◽  
Microbial Infection ◽  
Immune Reactions ◽  
Content Type ◽  
Essential Components ◽  
Stimulation Of

ABSTRACTPathogen recognition receptors (PRRs) are essential components of host innate immune systems that detect specific conserved pathogen-associated molecular patterns (PAMPs) presented by microorganisms. Members of two families of PRRs, transmembrane Toll-like receptors (TLRs 1, 2, 4, 5, and 6) and cytosolic NOD receptors (NOD1 and NOD2), are stimulated upon recognition of various bacterial PAMPs. Such stimulation leads to induction of a number of immune defense reactions, mainly triggered via activation of the transcription factor NF-κB. While coordination of responses initiated via different PRRs sensing multiple PAMPS present during an infection makes clear biological sense for the host, such interactions have not been fully characterized. Here, we demonstrate that combined stimulation of NOD1 and TLR5 (as well as other NOD and TLR family members) strongly potentiates activity of NF-κB and induces enhanced levels of innate immune reactions (e.g., cytokine production) bothin vitroandin vivo. Moreover, we show that an increased level of NF-κB activity plays a critical role in formation of downstream responses. In live mice, synergy between these receptors resulting in potentiation of NF-κB activity was organ specific, being most prominent in the gastrointestinal tract. Coordinated activity of NOD1 and TLR5 significantly increased protection of mice against enteroinvasiveSalmonellainfection. Obtained results suggest that cooperation of NOD and TLR receptors is important for effective responses to microbial infectionin vivo.

Role of copper in defending against bacterial infection

2015 ◽  
Author(s):  
◽  
Erik Ladomersky
Keyword(s):  
Bacterial Infection ◽  
Host Defense ◽  
Immune Defense ◽  
Copper Proteins ◽  
University Of Missouri ◽  
Susceptibility To Infection ◽  
Essential Nutrient ◽  
The University ◽  
The Relationship

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Copper is an essential nutrient. It plays an important role in development, pigmentation, neurological function, and immune defense. Copper deficiency is known to make host's more susceptible to infection. In this work we show that two copper proteins, ATP7A and ceruloplasmin, are important for host defense against bacterial infection. Studies have shown ATP7A is responsible for increasing copper concentrations inside the phagosome. Our study sheds light on the role of Atp7a and copper in adaptive immunity, and provide a biochemical model for understanding the relationship between copper malnutrition and susceptibility to infection. Iron, another essential nutrient, is linked with copper through the actions of copper-dependent proteins which play a role in maintaining normal iron levels in the blood. One of these proteins is ceruloplasmin, a protein that is also upregulated during infection. Our study sheds light onto why this protein is necessary for host defense against Salmonella infection.

Abstract WP389: Anatomical Trajectory for Focused Ultrasound Stimulation of Fastigial Nucleus for Neuroprotection in Human Cerebral Ischemia

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mersedeh Bahr Hosseini ◽  
Norman Spivak ◽  
Martin Monti ◽  
Alex Korb ◽  
Jeffrey L Saver
Keyword(s):  
Ischemic Stroke ◽  
Focused Ultrasound ◽  
Brain Mri ◽  
Skin Surface ◽  
Fastigial Nucleus ◽  
Neutral Position ◽  
Neck Flexion ◽  
Ultrasound Stimulation ◽  
The Mean ◽  
Stimulation Of

Introduction: In multiple animal models of ischemic stroke, cerebellar fastigial nucleus stimulation (FNS) via implanted electrode has been shown to exert strong neuroprotective and collateral enhancement effects. Translational studies of FNS have been precluded due to the invasive nature of direct electrical stimulation. Recently, low-intensity focused ultrasound pulsation (LIFUP) has been used to stimulate deep hemispheric targets. Identifying achievable anatomic trajectories for LIFUP delivery is required for human trials. Method: Sagittal brain MRI T1 from 10 patients were analyzed. Potential pathways from the suboccipital (SO) region (transducer placement site) to the roof of the 4 th ventricle (location of FN) were traced, evaluating paths both via the thinnest portion of the occipital bone (OB) and via the transforaminal window (TFW). Interindividual variations in trajectory distances (cm), thickness of the OB through which the beam passes (cm), and the projected neck flexion degree from neutral position required to achieve a TFW path were measured. Results: An achievable anatomic pathway for stimulation of the FN via LIFUP was identified in 100% of patients (Fig 1). In standard MR positioning, 90% had an available path through thin portions of the OB and 10% had a projected path through TFW. The mean distance from the skin at the SO region to the roof of 4 th ventricle/FN was 7.2 cm (± 0.64cm). The mean OB thickness traversed by the beam was 0.3cm (±0.1). The projected required neck flexion to enable a TFW in all subjects was mean 9.3° (±5°). Conclusions: The distance for the LIFUP beam to travel from skin surface to FN via a suboccipital approach is well within the LIFUP penetration depth and all individuals had an accessible trajectory via the TFW through attainable degrees of head flexion, affording minimal ultrasonic energy dispersion and maximal focality. Ultrasound stimulation of fastigial nucleus is a feasible treatment strategy in human acute ischemic stroke.

scholarly journals CRISPR Interference Limits Horizontal Gene Transfer in Staphylococci by Targeting DNA

Science ◽  
2008 ◽  
Vol 322 (5909) ◽  
pp. 1843-1845 ◽  
Author(s):  
Luciano A. Marraffini ◽  
Erik J. Sontheimer
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Staphylococcus Epidermidis ◽  
Pathogenic Bacteria ◽  
Target Sequence ◽  
Crispr Interference ◽  
Multiple Routes ◽  
Short Palindromic Repeat ◽  
Self Splicing

Horizontal gene transfer (HGT) in bacteria and archaea occurs through phage transduction, transformation, or conjugation, and the latter is particularly important for the spread of antibiotic resistance. Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci confer sequence-directed immunity against phages. A clinical isolate ofStaphylococcus epidermidisharbors a CRISPR spacer that matches thenickasegene present in nearly all staphylococcal conjugative plasmids. Here we show that CRISPR interference prevents conjugation and plasmid transformation inS. epidermidis. Insertion of a self-splicing intron intonickaseblocks interference despite the reconstitution of the target sequence in the spliced mRNA, which indicates that the interference machinery targets DNA directly. We conclude that CRISPR loci counteract multiple routes of HGT and can limit the spread of antibiotic resistance in pathogenic bacteria.

scholarly journals Host PGRP Gene Expression and Bacterial Release in Endosymbiosis of the Weevil Sitophilus zeamais

2006 ◽  
Vol 72 (10) ◽  
pp. 6766-6772 ◽  
Author(s):  
Caroline Anselme ◽  
Agnès Vallier ◽  
Séverine Balmand ◽  
Marie-Odile Fauvarque ◽  
Abdelaziz Heddi
Keyword(s):  
State Level ◽  
Immune Defense ◽  
Sitophilus Zeamais ◽  
Host Immune System ◽  
Gene Transcript ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Peptidoglycan Recognition Protein ◽  
Reverse Transcription Pcr ◽  
Imd Pathway

ABSTRACT Intracellular symbiosis (endosymbiosis) with gram-negative bacteria is common in insects, yet little is known about how the host immune system perceives the endosymbionts and controls their growth and invasion without complete bacterial clearance. In this study, we have explored the expression of a peptidoglycan recognition protein gene of the weevil Sitophilus zeamais (wPGRP); an ortholog in Drosophila (i.e., PGRP-LB) was recently shown to downregulate the Imd pathway (A. Zaidman-Remy, M. Herve, M. Poidevin, S. Pili-Floury, M. S. Kim, D. Blanot, B. H. Oh, R. Ueda, D. Mengin-Lecreulx, and B. Lemaitre, Immunity 24:463-473, 2006). Insect challenges with bacteria have demonstrated that wPGRP is induced by gram-negative bacteria and that the level of induction depends on bacterial growth. Real-time reverse transcription-PCR quantification of the wPGRP gene transcript performed at different points in insect development has shown a high steady-state level in the bacteria-bearing organ (the bacteriome) of larvae and a high level of wPGRP up-regulation in the symbiotic nymphal phase. Concomitantly, during this stage fluorescence in situ hybridization has revealed an endosymbiont release from the host bacteriocytes. Together with the previously described high induction level of endosymbiont virulence genes at the nymphal phase (C. Dale, G. R. Plague, B. Wang, H. Ochman, and N. A. Moran, Proc. Natl. Acad. Sci. USA 99:12397-12402, 2002), these findings indicate that insect mutualistic relationships evolve through an interplay between bacterial virulence and host immune defense and that the host immunity engages the PGRP gene family in that interplay.

Trichobilharzia ocellata: chemical stimuli of duck skin for cercarial attachment

Parasitology ◽  
1988 ◽  
Vol 96 (3) ◽  
pp. 507-517 ◽  
Author(s):  
W. Feiler ◽  
W. Haas
Keyword(s):  
Close Contact ◽  
Skin Surface ◽  
Preen Gland ◽  
Surface Lipids ◽  
Skin Surface Lipids ◽  
Chemical Stimuli ◽  
Host Identification ◽  
Host Signals ◽  
Trichobilharzia Ocellata ◽  
Stimulation Of

SUMMARYTrichobilharzia ocellatacercariae attach readily to the foot skin of their duck host, but poorly to preen-gland contents. The attachment to duck foot disappears when the skin surface lipids are extracted, and can be restored by reapplication of the lipids to the skin. Hydrophilic skin extracts are without any effect. Thin-layer chromatographic fractionation of duck-foot skin surface lipids reveals cholesterol and ceramides as attachment stimuli. A stimulation of cercarial attachment by these hydrophobic host signals is supported by the host identification pattern of the cercariae, which secures a close contact with encountered substrates.

scholarly journals Transcriptional Regulation oficaADBCby both IcaR and TcaR inStaphylococcus epidermidis

2019 ◽  
Vol 201 (6) ◽  
Author(s):  
Tra-My Hoang ◽  
C. Zhou ◽  
J. K. Lindgren ◽  
M. R. Galac ◽  
B. Corey ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Constitutive Expression ◽  
Skin Surface ◽  
Fine Tuning ◽  
Transcriptional Repressors ◽  
Content Type ◽  
Expression Levels ◽  
Dnase I Footprinting ◽  
Genetic Mechanisms ◽  
Operon Expression

ABSTRACTS. epidermidisis a primary cause of biofilm-mediated infections in humans due to adherence to foreign bodies. A major staphylococcal biofilm accumulation molecule is polysaccharide intracellular adhesin (PIA), which is synthesized by enzymes encoded by theicaADBCoperon. Expression of PIA is highly variable among clinical isolates, suggesting that PIA expression levels are selected in certain niches of the host. However, the mechanisms that govern enhancedicaADBCtranscription and PIA synthesis in these isolates are not known. We hypothesized that enhanced PIA synthesis in these isolates was due to function of IcaR and/or TcaR. Thus, twoS. epidermidisisolates (1457 and CSF41498) with differenticaADBCtranscription and PIA expression levels were studied. Constitutive expression of bothicaRandtcaRdemonstrated that both repressors are functional and can completely repressicaADBCtranscription in both 1457 and CSF41498. However, it was found that IcaR was the primary repressor for CSF41498 and TcaR was the primary repressor for 1457. Further analysis demonstrated thaticaRtranscription was repressed in 1457 in comparison to CSF41498, suggesting that TcaR functions as a repressor only in the absence of IcaR. Indeed, DNase I footprinting suggests IcaR and TcaR may bind to the same site within theicaR-icaAintergenic region. Lastly, we found mutants expressing variable amounts of PIA could rapidly be selected from both 1457 and CSF41498. Collectively, we propose that strains producing enhanced PIA synthesis are selected within certain niches of the host through several genetic mechanisms that function to repressicaRtranscription, thus increasing PIA synthesis.IMPORTANCEStaphylococcus epidermidisis a commensal bacterium that resides on our skin. As a commensal, it protects humans from bacterial pathogens through a variety of mechanisms. However, it is also a significant cause of biofilm infections due to its ability to bind to plastic. Polysaccharide intercellular adhesin is a significant component of biofilm, and we propose that the expression of this polysaccharide is beneficial in certain host niches, such as providing extra strength when the bacterium is colonizing the lumen of a catheter, and detrimental in others, such as colonization of the skin surface. We show here that fine-tuning oficaADBCtranscription, and thus PIA synthesis, is mediated via two transcriptional repressors, IcaR and TcaR.

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