scholarly journals Neonatal granulocytic MDSCs possess phagocytic properties during bacterial infection

2019 ◽  
Author(s):  
Brittany G. Seman ◽  
Jordan K. Vance ◽  
Michelle R. Witt ◽  
Cory M. Robinson
Keyword(s):  
Bacterial Infection ◽  
Acute Infection ◽  
Suppressor Cells ◽  
Extracellular Dna ◽  
Phagocytic Capacity ◽  
E Coli ◽  
Susceptibility To Infection ◽  
Immunosuppressive Cell ◽  
Gene And Protein Expression ◽  
Bacterial Uptake

AbstractMyeloid-derived suppressor cells (MDSCs) are an immunosuppressive cell type found in high abundance in early life. Currently, there has been limited mechanistic understanding of MDSC phagocytosis of bacteria and the corresponding consequences in the context of acute infection. We set out to determine whether human granulocytic MDSCs have phagocytic capacity that is comparable to other professional phagocytes. To investigate these properties, we utilized fluorescent confocal microscopy, flow cytometry, and bacterial burden assays. We demonstrate that human granulocytic MDSCs phagocytose E. coli O1:K1:H7, and subsequently traffic the bacteria into acidic compartments similar to other phagocytes. However, MDSCs were significantly less efficient at bacterial uptake and killing compared to monocytes. This activity is associated with an inflammatory response, but the amount of TNFα gene and protein expression was reduced in infected MDSCs compared to monocytes. Interestingly, we also found that MDSCs release DNA (MeDNA) into the extracellular space that resembles neutrophil extracellular traps. We found that MeDNA had some impact on bacterial viability in single cultures, with an increase in bacterial recovery in MDSCs treated with DNAse. However, MeDNA did not impact the ability of monocytes to eliminate bacteria in co-cultures, suggesting that MDSC extracellular DNA does not compromise monocyte function. Overall, our data reveals mechanistic insight into MDSC activity during infection that includes the kinetics and efficiency of bacterial uptake, elimination through trafficking to acidified compartments, and inflammatory contributions relative to primary human monocytes. These results enhance our understanding of MDSC contributions during acute bacterial infection and identify host-directed targets for immune intervention to improve outcomes and reduce susceptibility to infection early in life.

scholarly journals Neonatal low-density granulocytes internalize and kill bacteria but suppress monocyte function using extracellular DNA

2021 ◽  
pp. jcs.252528
Author(s):  
Brittany G. Seman ◽  
Jordan K. Vance ◽  
Stephen M. Akers ◽  
Cory M. Robinson
Keyword(s):  
Acute Infection ◽  
Mononuclear Phagocytes ◽  
Extracellular Dna ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Low Density ◽  
E Coli ◽  
Host Protection ◽  
Bacterial Uptake ◽  
Inflammatory Cytokine Response

Low-density granulocytes (LDGs) are found abundantly in neonatal blood. However, there is limited mechanistic understanding of LDG interactions with bacteria and innate immune cells during acute infection. We aimed to determine how human neonatal LDGs may influence control of the bacterial burden at sites of infection, both individually and in the presence of mononuclear phagocytes. LDGs from human umbilical cord blood do phagocytose E. coli O1:K1:H7 and traffic bacteria into acidic compartments. However, LDGs were significantly less efficient at bacterial uptake and killing compared to monocytes, and this activity was associated with a reduced inflammatory cytokine response. The presence of bacteria triggered the release of DNA (eDNA) from LDGs into the extracellular space that resembled neutrophil extracellular traps, but had limited anti-bacterial activity. Instead, eDNA significantly impaired monocyte control of bacteria during co-culture. These results suggest that LDG recruitment to sites of bacterial infection may compromise host protection in the neonate. Furthermore, our findings reveal novel insights into LDG activity during infection, clarify inflammatory contributions relative to monocytes, and identify a novel LDG mechanism of immunosuppression.

Relationship of antibiotic resistance to results of treatment in sepsis patients in Hue Central Hospital 2017 – 2018

2019 ◽  
pp. 48-54
Author(s):  
Duy Binh Nguyen ◽  
Trung Tien Phan ◽  
Trong Hanh Hoang ◽  
Van Tuan Mai ◽  
Xuan Chuong Tran
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infection ◽  
Resistant Bacteria ◽  
Central Hospital ◽  
International Consensus ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Results Of Treatment ◽  
Amoxicillin Clavulanic Acid ◽  
Relationship Of

Sepsis is a serious bacterial infection. The main treatment is using antibiotics. However, the rate of antibiotic resistance is very high and this resistance is related to the outcome of treatment. Objectives: To evaluate the situation of antibiotic resistance of some isolated bacteria in sepsis patients treated at Hue Central Hospital; to evaluate the relationship of antibiotic resistance to the treatment results in patients with sepsis. Subjects and methods: prospective study of 60 sepsis patients diagnosed according to the criteria of the 3rd International Consensus-Sepsis 3 and its susceptibility patterns from April 2017 to August 2018. Results and Conclusions: The current agents of sepsis are mainly S. suis, Burkhoderiae spp. and E. coli. E. coli is resistant to cephalosporins 3rd, 4th generation and quinolone group is over 75%; resistance to imipenem 11.1%; the ESBL rate is 60%. S. suis resistant to ampicilline 11.1%; no resistance has been recorded to ceftriaxone and vancomycine. Resistance of Burkholderiae spp. to cefepime and amoxicillin/clavulanic acid was 42.9% and 55.6%, resistant to imipenem and meropenem is 20%, resistance to ceftazidime was not recorded. The deaths were mostly dued to E. coli and K. pneumoniae. The mortality for patients infected with antibiotic-resistant bacteria are higher than for sensitive groups. Key words: Sepsis, bacterial infection, antibiotics

scholarly journals Myeloid-Derived Suppressor Cells and Pancreatic Cancer: Implications in Novel Therapeutic Approaches

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1627 ◽  
Author(s):  
Anita Thyagarajan ◽  
Mamdouh Salman A. Alshehri ◽  
Kelly L.R. Miller ◽  
Catherine M. Sherwin ◽  
Jeffrey B. Travers ◽  
...  
Keyword(s):  
Survival Rates ◽  
Suppressor Cells ◽  
Cell Types ◽  
Therapeutic Agents ◽  
Ductal Adenocarcinoma ◽  
Cancer Therapies ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Resistance ◽  
Cellular Mechanisms ◽  
Immunosuppressive Cell

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating human malignancy with poor prognosis and low survival rates. Several cellular mechanisms have been linked with pancreatic carcinogenesis and also implicated in inducing tumor resistance to known therapeutic regimens. Of various factors, immune evasion mechanisms play critical roles in tumor progression and impeding the efficacy of cancer therapies including PDAC. Among immunosuppressive cell types, myeloid-derived suppressor cells (MDSCs) have been extensively studied and demonstrated to not only support PDAC development but also hamper the anti-tumor immune responses elicited by therapeutic agents. Notably, recent efforts have been directed in devising novel approaches to target MDSCs to limit their effects. Multiple strategies including immune-based approaches have been explored either alone or in combination with therapeutic agents to target MDSCs in preclinical and clinical settings of PDAC. The current review highlights the roles and mechanisms of MDSCs as well as the implications of this immunomodulatory cell type as a potential target to improve the efficacy of therapeutic regimens for PDAC.

scholarly journals PSVIII-8 Effect of Lactobacillus Casei Zhang on E. coli induced injury of blood and milk barrier in dairy cow

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 259-259
Author(s):  
Yuhui Zheng ◽  
Shengli Li
Keyword(s):  
Bacterial Infection ◽  
Lactobacillus Casei ◽  
Bacterial Resistance ◽  
Bovine Mastitis ◽  
Production Performance ◽  
Economic Losses ◽  
Control Group ◽  
Bovine Mammary Epithelial Cells ◽  
E Coli ◽  
Lactobacillus Casei Zhang

Abstract Bovine mastitis is one of the major diseases which directly affects the milk production performance and it causes huge economic losses in the dairy industry. Bacterial infection is the main risk factor of bovine mastitis and the antibiotic therapy is the primary choice to control the disease. However, persistence use of antibiotic increases the incidence of bacterial resistance and traces of antibiotic residues in animal products. Lactobacillus casei Zhang is one of the probiotics with multiple biological functions, which has certain bacteriostatic effect on pathogenic microorganism. The purpose of this study was to explore the effect of Lactobacillus casei Zhang (L. casei Zhang) on the prevention of E. coli-induced milk-blood barrier damage. Bovine mammary epithelial cells (BMECs) were used to establish a milk-blood model and Control group (PBS), E. coli group, and L. casei Zhang pretreatment plus E. coli group were set up respectively. The results showed that: L. casei Zhang could significantly reduce the increase of LDH release caused by E. coli treatment (P< 0.05). And it can also significantly reduce the decrease of transmembrane resistance of monolayer cells caused by E. coli treatment (P< 0.05). In addition, L. casei Zhang could significantly reduce the expression of tight junction proteins ZO-1, Claudin-1, Claudin-4 and Occludin (P < 0.05). In conclusion, L. casei Zhang could effectively improve the damage of the blood-milk barrier caused by E. coli and could protect BMECs during bacterial infection.

Long-Haul Transport and Lack of Preconditioning Increases Fecal Shedding of Escherichia coli and Escherichia coli O157:H7 by Calves†

2004 ◽  
Vol 67 (4) ◽  
pp. 672-678 ◽  
Author(s):  
S. J. BACH ◽  
T. A. McALLISTER ◽  
G. J. MEARS ◽  
K. S. SCHWARTZKOPF-GENSWEIN
Keyword(s):  
Escherichia Coli ◽  
Escherichia Coli O157 ◽  
Fecal Samples ◽  
Fecal Shedding ◽  
E Coli ◽  
Susceptibility To Infection

The effects of weaning and transport on fecal shedding of Escherichia coli and on E. coli O157:H7 were investigated using 80 Angus and 94 Charolais range steer calves blocked by breed and assigned to four treatments. The calves were or were not preconditioned before transport on commercial cattle liner to the feedlot via long (15 h) or short (3 h) hauling duration, yielding preconditioned long haul (P-L; n = 44), preconditioned short haul (P-S; n = 44), nonpreconditioned long haul (NP-L; n = 43), and nonpreconditioned short haul (NP-S; n = 43). Preconditioned calves were vaccinated and weaned 29 and 13 days, respectively, before transport. Nonpreconditioned calves were weaned 1 day before long or short hauling, penned for 24 h and hauled again for 2 h, and vaccinated on arrival at the feedlot. Fecal samples were collected from calves while on pasture, at weaning, at loading for transport, on arrival at the feedlot, twice in the first week, and on days 7, 14, 21, and 28 for enumeration of total E. coli (biotype 1) and detection of E. coli O157:H7. No calves were positive for E. coli O157:H7 before transport. Following transport, more (P < 0.005) NP-L calves (6 of 43) tested positive for E. coli O157:H7 than did P-L (1 of 44), NP-S (1 of 43), or P-S (0 of 44) calves, and on days 0, 1, 7, and 21, their levels of shedding of E. coli were higher (P < 0.005). The calves' susceptibility to infection from the environment (possibly the holding facilities or feedlot pens) was likely elevated by the stresses of weaning, transport, and relocation. Lack of preconditioning and long periods of transport (NP-L) increased fecal shedding of E. coli and E. coli O157:H7. Preconditioning may serve to reduce E. coli O157:H7 shedding by range calves on arrival at the feedlot.

scholarly journals Intestinal Metabolites Influence Macrophage Phagocytosis and Clearance of Bacterial Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Amy A. O’Callaghan ◽  
Elaine Dempsey ◽  
Namrata Iyer ◽  
Sarah Stiegeler ◽  
Kevin Mercurio ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Metabolic Flux ◽  
Marker Gene ◽  
Intestinal Lumen ◽  
Microbial Fermentation ◽  
Macrophage Phenotype ◽  
E Coli ◽  
Macrophage Phagocytosis ◽  
Infection Treatment ◽  
By Products

The metabolite-rich environment that is the intestinal lumen contains metabolic by-products deriving from microbial fermentation and host cell metabolism, with resident macrophages being constantly exposed to this metabolic flux. Succinate, lactate and itaconate are three metabolites secreted by primed macrophages due to a fragmented tri-carboxylic acid (TCA) cycle. Additionally, succinate and lactate are known by-products of microbial fermentation. How these metabolites impact biological functioning of resident macrophages particularly in response to bacterial infection remains poorly understood. We have investigated the potential influence of these metabolites on macrophage phagocytosis and clearance of Escherichia coli (E. coli) infection. Treatment of murine bone-marrow-derived macrophages (BMDMs) with succinate reduced numbers of intracellular E. coli early during infection, while lactate-treated BMDMs displayed no difference throughout the course of infection. Treatment of BMDMs with itaconate lead to higher levels of intracellular E. coli early in the infection with bacterial burden subsequently reduced at later time-points compared to untreated macrophages, indicative of enhanced engulfment and killing capabilities of macrophages in response to itaconate. Expression of engulfment mediators MARCKS, RhoB, and CDC42 were reduced or unchanged following succinate or lactate treatment and increased in itaconate-treated macrophages following E. coli infection. Nitric oxide (NO) levels varied while pro- and anti-inflammatory cytokines differed in secretory levels in all metabolite-treated macrophages post-infection with E. coli or in response to lipopolysaccharide (LPS) stimulation. Finally, the basal phenotypic profile of metabolite-treated macrophages was altered according to marker gene expression, describing how fluid macrophage phenotype can be in response to the microenvironment. Collectively, our data suggests that microbe- and host-derived metabolites can drive distinct macrophage functional phenotypes in response to infection, whereby succinate and itaconate regulate phagocytosis and bactericidal mechanisms, limiting the intracellular bacterial niche and impeding the pathogenesis of infection.

scholarly journals Escherichia coli Competence Gene Homologs Are Essential for Competitive Fitness and the Use of DNA as a Nutrient

2006 ◽  
Vol 188 (11) ◽  
pp. 3902-3910 ◽  
Author(s):  
Vyacheslav Palchevskiy ◽  
Steven E. Finkel
Keyword(s):  
Escherichia Coli ◽  
Sole Source ◽  
Extracellular Dna ◽  
Nutrient Source ◽  
Genetic Competence ◽  
Exogenous Dna ◽  
Competitive Fitness ◽  
E Coli ◽  
Widespread Phenomenon

ABSTRACT Natural genetic competence is the ability of cells to take up extracellular DNA and is an important mechanism for horizontal gene transfer. Another potential benefit of natural competence is that exogenous DNA can serve as a nutrient source for starving bacteria because the ability to “eat” DNA is necessary for competitive survival in environments containing limited nutrients. We show here that eight Escherichia coli genes, identified as homologs of com genes in Haemophilus influenzae and Neisseria gonorrhoeae, are necessary for the use of extracellular DNA as the sole source of carbon and energy. These genes also confer a competitive advantage to E. coli during long-term stationary-phase incubation. We also show that homologs of these genes are found throughout the proteobacteria, suggesting that the use of DNA as a nutrient may be a widespread phenomenon.

Dissociation of zinc phthalocyanine aggregation on bacterial surface is key for photodynamic antimicrobial effect

2018 ◽  
Vol 22 (09n10) ◽  
pp. 925-934 ◽  
Author(s):  
Dafeng Liu ◽  
Linsen Li ◽  
Jincan Chen ◽  
Zhuo Chen ◽  
Longguang Jiang ◽  
...  
Keyword(s):  
Antimicrobial Effect ◽  
Antibacterial Activities ◽  
Surface Hydrophobicity ◽  
The Other ◽  
Zinc Phthalocyanine ◽  
Bacterial Surface ◽  
E Coli ◽  
Bacterial Signaling ◽  
Bacterial Uptake ◽  
Key Parameter

Antimicrobial photodynamic therapy (aPDT) is an effective mean for killing bacteria in this era of increasing multi-antibiotic resistance, and possesses a number of unique advantages. Much effort has been devoted to the development a key component of aPDT photosensitizers (PSs). We synthesized a series of PSs with different positive charges (ZnPc(Lys)[Formula: see text], where [Formula: see text] 3, 5, 7, and studied their antibacterial activities and mechanisms against Escherichia coli (E. coli). Interestingly, the ZnPc(Lys)[Formula: see text] derivative showed stronger antibacterial effect (MIC = 25.3 [Formula: see text]M) than the other two PSs (MICs = 50.6 [Formula: see text]M), even though this PS did not have the highest uptake on bacteria among these PSs. It was ZnPc(Lys)[Formula: see text] that possessed the highest bacterial uptake. ZnPc(Lys)[Formula: see text] was found to have the highest monomeric fractions (62.0%) on bacteria surface than the other two PSs (37.9% for [Formula: see text] 3 and 33.9% [Formula: see text] = 7). These results clearly demonstrate that PS conformation on bacterial surface as a key parameter determining antibacterial efficacy of PSs. Other mechanistic aspects of photodynamic effects, including PS binding kinetics, bacterial surface hydrophobicity, zeta potential of bacteria, membrane permeability and bacterial signaling pathways were also studied.

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 87: The Accumulation of Myeloid-derived Suppressor Cells Is a Compensatory Response to the Development of Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Xiao Z Shen ◽  
Peng Shi ◽  
Jorge Giani ◽  
Ellen Bernstein ◽  
Kenneth E Bernstein
Keyword(s):  
Blood Pressure ◽  
T Cell ◽  
Angiotensin Ii ◽  
Critical Role ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Compensatory Response ◽  
Immunosuppressive Cell ◽  
Induced Hypertension

The immune system plays a critical role in the development of hypertension. The immune response consists of pro-inflammatory cells, but also immunosuppressive cells that reduce T cell function. An important category of natural immunosuppressive cell is myeloid-derived suppressor cells (MDSC). We now show that blood and spleen CD11b+ Gr1+ myeloid cells are elevated 2-fold in both angiotensin II and L-NAME induced hypertension. These increased myeloid cells are MDSC in that they elevate IL-4R expression and suppress T cell proliferation. When hypertensive mice were depleted of MDSC, using either anti-Gr1 antibody or gemcitabine, there was a 15 mmHg rise in blood pressure and aggravation of T cells activation with increased production of IFN-γ, TNFα and IL-17 in both spleen and kidney. In contrast, adoptive transfer of MDSC reduced blood pressure in angiotensin-II induced hypertension by 25 mmHg (see Figure). These data suggest a new concept, that the accumulation of MDSC is a compensatory response to the inflammation induced by hypertension. They also indicate that MDSC play an important role in regulating blood pressure.

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