The Phagocyte Oxidase Controls Tolerance toMycobacterium tuberculosisinfection

SummaryProtection from infectious disease relies on two distinct mechanisms. “Antimicrobial resistance” directly inhibits pathogen growth, whereas “infection tolerance” controls tissue damage. A single immune-mediator can differentially contribute to these mechanisms in distinct contexts, confounding our understanding of protection to different pathogens. For example, the NADPH-dependent phagocyte oxidase complex (Phox) produces anti-microbial superoxides and protects from tuberculosis in humans. However, Phox-deficient mice do not display the expected defect in resistance toM. tuberculosisleaving the role of this complex unclear. We re-examined the mechanisms by which Phox contributes to protection from TB and found that mice lacking the Cybb subunit of Phox suffered from a specific defect in tolerance, which was due to unregulated Caspase1 activation, IL-1β production, and neutrophil influx into the lung. These studies demonstrate that Phox-derived superoxide protect against TB by promoting tolerance to persistent infection, and highlight a central role for Caspase1 in regulating TB disease progression.

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S100A8/A9 modulates inflammatory collateral tissue damage during intraperitoneal origin systemic candidiasis

10.1101/2020.03.30.017491 ◽

2020 ◽

Author(s):

Madhu Shankar ◽

Nathalie Uwamahoro ◽

Sandra Holmberg ◽

Maria Joanna Niemiec ◽

Johannes Roth ◽

...

Keyword(s):

Tissue Damage ◽

Critical Role ◽

Specific Inhibitor ◽

Surgical Intensive Care ◽

Inflammatory Protein ◽

Systemic Level ◽

Combating Infection ◽

Deficient Mice

AbstractPeritonitis is a leading cause of severe sepsis in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial, pro-inflammatory protein complex often used as a biomarker for diagnosis of disease activities in many inflammatory disorders. Here we describe the role of S100A8/A9 on inflammatory collateral tissue damage (ICTD).We performed an in vivo Candida albicans disseminated peritonitis mouse model using WT and S100A9-deficient mice and stimulated primary macrophages with recombinant S100A8/A9 in the presence or absence of the compound paquinimod, a specific inhibitor of S100A9. In addition, the effects on ICTD and fungal clearance were investigated. S100A9-deficient mice developed less ICTD than wildtype mice. Restoration of S100A8/A9 in S100A9 knockout mice resulted in increased ICTD and fungal clearance comparable to wildtype levels. Treatment with paquinimod abolished ICTD.The data indicated that S100A8/A9 controls ICTD levels and host antimicrobial modulation at a systemic level during intra-abdominal candidiasis (IAC).

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Bacteriocins: antibiotics in the age of the microbiome

Emerging Topics in Life Sciences ◽

10.1042/etls20160015 ◽

2017 ◽

Vol 1 (1) ◽

pp. 55-63 ◽

Cited By ~ 9

Author(s):

Kevin Egan ◽

R. Paul Ross ◽

Colin Hill

Keyword(s):

Infectious Disease ◽

Animal Models ◽

Antimicrobial Resistance ◽

Animal Health ◽

Collateral Damage ◽

Safety And Efficacy ◽

Antibiotic Development ◽

The Impact ◽

Activity Animal

Antibiotics have revolutionised the treatment of infectious disease and improved the lives of billions of people worldwide over many decades. With the rise in antimicrobial resistance (AMR) and corresponding lack of antibiotic development, we find ourselves in dire need of alternative treatments. Bacteriocins are a class of bacterially produced, ribosomally synthesised, antimicrobial peptides that may be narrow or broad in their spectra of activity. Animal models have demonstrated the safety and efficacy of bacteriocins in treating a broad range of infections; however, one of the principal drawbacks has been their relatively narrow spectra when compared with small-molecule antibiotics. In an era where we are beginning to appreciate the role of the microbiota in human and animal health, the fact that bacteriocins cause much less collateral damage to the host microbiome makes them a highly desirable therapeutic. This review makes a case for the implementation of bacteriocins as therapeutic antimicrobials, either alone or in combination with existing antibiotics to alleviate the AMR crisis and to lessen the impact of antibiotics on the host microbiome.

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Decades of emerging infectious disease, food safety, and antimicrobial resistance response in Vietnam: The role of One Health

One Health ◽

10.1016/j.onehlt.2021.100361 ◽

2021 ◽

pp. 100361

Author(s):

Hung Nguyen-Viet ◽

Steven Lam ◽

Huong Nguyen-Mai ◽

Dao Thu Trang ◽

Vu Thi Phuong ◽

...

Keyword(s):

Infectious Disease ◽

Food Safety ◽

Antimicrobial Resistance ◽

One Health ◽

Emerging Infectious Disease ◽

Resistance Response

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Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis

Frontiers in Immunology ◽

10.3389/fimmu.2021.553911 ◽

2021 ◽

Vol 12 ◽

Author(s):

Madhu Shankar ◽

Nathalie Uwamahoro ◽

Emelie Backman ◽

Sandra Holmberg ◽

Maria Joanna Niemiec ◽

...

Keyword(s):

Tissue Damage ◽

Severe Disease ◽

Critical Role ◽

Wild Type ◽

Surgical Intensive Care ◽

Fungal Peritonitis ◽

Inflammatory Protein ◽

Intra Abdominal Infection ◽

Deficient Mice

Intra-abdominal infection (peritonitis) is a leading cause of severe disease in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial and pro-inflammatory protein complex used as a biomarker for diagnosis of numerous inflammatory disorders. Here we describe the role of S100A8/A9 in inflammatory collateral tissue damage (ICTD). Using a mouse model of disseminated intra-abdominal candidiasis (IAC) in wild-type and S100A8/A9-deficient mice in the presence or absence of S100A9 inhibitor paquinimod, the role of S100A8/A9 during ICTD and fungal clearance were investigated. S100A8/A9-deficient mice developed less ICTD than wild-type mice. Restoration of S100A8/A9 in knockout mice by injection of recombinant protein resulted in increased ICTD and fungal clearance comparable to wild-type levels. Treatment with paquinimod abolished ICTD and S100A9-deficient mice showed increased survival compared to wild-type littermates. The data indicates that S100A8/A9 controls ICTD levels and antimicrobial activity during IAC and that targeting of S100A8/A9 could serve as promising adjunct therapy against this challenging disease.

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The role of macrophage scavenger receptor 1 (Msr1) in prion pathogenesis

10.1101/2020.11.17.386433 ◽

2020 ◽

Author(s):

Bei Li ◽

Meiling Chen ◽

Adriano Aguzzi ◽

Caihong Zhu

Keyword(s):

Disease Progression ◽

Infected Mouse ◽

Prion Diseases ◽

Scavenger Receptor ◽

Amyloid Β ◽

Wild Type ◽

Macrophage Scavenger Receptor ◽

The Brain ◽

Deficient Mice

AbstractThe progression of prion diseases is accompanied by the accumulation of prions in the brain. Ablation of microglia enhances prion accumulation and accelerates disease progression, suggesting that microglia play a neuroprotective role by clearing prions. However, the mechanisms underlying the phagocytosis and clearance of prion are largely unknown. The macrophage scavenger receptor 1 (Msr1) is an important phagocytic receptor expressed by microglia in the brain, and is involved in the uptake and clearance of soluble amyloid-β. We therefore asked whether Msr1 might play a role in prion clearance, and assessed the scavenger function of Msr1 in prion pathogenesis. We found that Msr1 expression was upregulated in prion-infected mouse brains. However, Msr1 deficiency did not change prion disease progression or lesion patterns. Prion deposition in Msr1 deficient mice was similar to their wild type littermates. In addition, prion-induced neuroinflammation was not affected by Msr1 ablation. We conclude that Msr1 does not play a major role in prion pathogenesis.

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Concerted regulation of non-alcoholic fatty liver disease progression by microRNAs in apolipoprotein E deficient mice

Disease Models & Mechanisms ◽

10.1242/dmm.049173 ◽

2021 ◽

Author(s):

Andrea R. López-Pastor ◽

Jorge Infante-Menéndez ◽

Tamara González Illanes ◽

Paula González-López ◽

Águeda González-Rodríguez ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Apolipoprotein E ◽

Disease Progression ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Altered Expression ◽

Deficient Mice ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) prevalence is constantly increasing and microRNAs (miRNAs) altered expression fosters the development and progression of many pathologies, including NAFLD. Therefore, we explored the role of new miRNAs involved in the molecular mechanisms that trigger NAFLD progression and evaluated them as biomarkers for diagnosis. As a NAFLD model, we used apolipoprotein E deficient mice submitted to high fat diet during 8 or 18 weeks. After 18 weeks on diet, we demonstrate that insulin resistance and decreased lipogenesis and autophagy are related to a concerted regulation carried out by miR-26b-5p, miR-34a-5p, miR-149-5p and miR-375-3p. We also propose circulating let-7d-5p and miR-146b-5p as potential biomarkers of early stages of NAFLD. Finally, we confirmed that circulating miR-34a-5p and miR-375-3p are elevated in the late stages and miR-27b-3p and miR-122-5p are increased with disease progression. Our results reveal a synergistic regulation by miRNAs of key processes in NAFLD development and progression. Finally, we propose new biomarkers for NAFLD diagnosis. Notwithstanding, more efforts are needed to unravel the role of these miRNAs for developing new strategies for NAFLD treatment.

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Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice

European Journal of Neuroscience ◽

10.1046/j.1460-9568.2000.01348.x ◽

2000 ◽

Vol 12 (12) ◽

pp. 4447-4456 ◽

Cited By ~ 24

Author(s):

Rose-Marie Bluthe ◽

Sophie Laye ◽

Bruno Michaud ◽

Chantal Combe ◽

Robert Dantzer ◽

...

Keyword(s):

Tumour Necrosis ◽

Interleukin 1 ◽

Tumour Necrosis Factor Alpha ◽

Type I ◽

Sickness Behaviour ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Deficient Mice ◽

Necrosis Factor

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Indian Lifestyle With Ayurveda Perspective During Covid-19 Pandemic

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11ispl1.3668 ◽

2020 ◽

Vol 11 (SPL1) ◽

pp. 1396-1399

Author(s):

Disha Bhatero ◽

Punam Sawarkar ◽

Gaurav Sawarkar

Keyword(s):

Infectious Disease ◽

Disease Resistance ◽

Prevalence Rate ◽

Code Of Conduct ◽

Google Scholar ◽

Research Articles ◽

Narrative Form ◽

Healthy Individuals ◽

Novel Coronavirus

Covid-19 is an infectious disease caused by novel Coronavirus. The overall prevalence rate of Covid-19 in Worldwide ( 9.94M )& it is (529 K) & (153 K) in India and Maharashtra. This situation can be considered under JanapadodhwansaVyadhi in Ayurveda. The primary purpose of Ayurveda is the prevention of the disease in healthy individuals and eradication of disease, which are curable. Immunity comes under the Vyadhikshamatva. Further, Covid-19 infection is correlated with Vataj-Kaphaj Jwara. In Ayurveda Rasayana therapy to boost up immunity (Bala & Vyadhikshamatva). The present study aimed to explore the concept of infectious disease and its prevention through different lifestyles described in Ayurveda. The above need-based information is collected from various Ayurvedicliterature (Laghutrayee, Bruhatryayi) along with numerous research articles from databases, such as PubMed, Google Scholar. All collected data were depicted in narrative form and tabular manner under different heads. Considering the above aspect in the prevention of Covid-19, the role of Ayurveda intervention may be proved more beneficial in Covid-19. Further, adoption of code of conduct may efficiently overcome the current pandemic situation by maintaining good immunity & implementation of Ahar, Vihar Vidhis, Dincharya, and Rutucharya& Sadvritta for improving disease resistance.

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