scholarly journals Innate Immunity as an Executor of the Programmed Death of Individual Organisms for the Benefit of the Entire Population

2021 ◽  
Vol 22 (24) ◽  
pp. 13480
Author(s):  
Boris V. Chernyak ◽  
Konstantin G. Lyamzaev ◽  
Armen Y. Mulkidjanian
Keyword(s):  
Innate Immunity ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Ischemia Reperfusion ◽  
Well Being ◽  
Defense Responses ◽  
Entire Population ◽  
Severe Illness ◽  
Major Goal ◽  
Programmed Death

In humans, over-activation of innate immunity in response to viral or bacterial infections often causes severe illness and death. Furthermore, similar mechanisms related to innate immunity can cause pathogenesis and death in sepsis, massive trauma (including surgery and burns), ischemia/reperfusion, some toxic lesions, and viral infections including COVID-19. Based on the reviewed observations, we suggest that such severe outcomes may be manifestations of a controlled suicidal strategy protecting the entire population from the spread of pathogens and from dangerous pathologies rather than an aberrant hyperstimulation of defense responses. We argue that innate immunity may be involved in the implementation of an altruistic programmed death of an organism aimed at increasing the well-being of the whole community. We discuss possible ways to suppress this atavistic program by interfering with innate immunity and suggest that combating this program should be a major goal of future medicine.

scholarly journals NHR-49/PPAR-α and HLH-30/TFEB promote C. elegans host defense via a flavin-containing monooxygenase

2020 ◽  
Author(s):  
Khursheed A. Wani ◽  
Debanjan Goswamy ◽  
Stefan Taubert ◽  
Ramesh Ratnappan ◽  
Arjumand Ghazi ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Host Defense ◽  
Bacterial Infections ◽  
Model Organism ◽  
Defense Responses ◽  
Cellular Level ◽  
Nuclear Hormone Receptor ◽  
Multiple Infection ◽  
C Elegans ◽  
Transcriptional Signature

SUMMARYDuring bacterial infection, the host is confronted with multiple overlapping signals that are integrated at the organismal level to produce defensive host responses. How multiple infection signals are sensed by the host and how they elicit the transcription of host defense genes is much less understood at the whole-animal level than at the cellular level. The model organism Caenorhabditis elegans is known to mount transcriptional defense responses against intestinal bacterial infections that elicit overlapping starvation and infection responses, but the regulation of such responses is not well understood. Direct comparison of C. elegans that were starved or infected with Staphylococcus aureus revealed a large infection-specific transcriptional signature. This signature was almost completely abrogated by deletion of transcription factor hlh-30/TFEB, except for six genes including a flavin-containing monooxygenase (FMO) gene, fmo-2/FMO5. Deletion of fmo-2/FMO5 severely compromised infection survival, thus identifying the first FMO with innate immunity functions in animals. Moreover, the mechanism of fmo-2/FMO5 induction required the nuclear hormone receptor, NHR-49/PPAR-α, which induced fmo-2/FMO5 and host defense cell non-autonomously. These findings for the first time reveal an infection-specific host response to S. aureus, identify HLH-30/TFEB as its main regulator, reveal that FMOs are important innate immunity effectors in animals, and identify the mechanism of FMO regulation through NHR-49/PPAR-α in C. elegans, with important implications for innate host defense in higher organisms.

scholarly journals NHR-49/PPAR-α and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Khursheed A Wani ◽  
Debanjan Goswamy ◽  
Stefan Taubert ◽  
Ramesh Ratnappan ◽  
Arjumand Ghazi ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Host Defense ◽  
Bacterial Infections ◽  
Model Organism ◽  
Defense Responses ◽  
Nuclear Hormone Receptor ◽  
C Elegans ◽  
Transcriptional Signature ◽  
Specific Host ◽  
Main Regulator

The model organism Caenorhabditis elegans mounts transcriptional defense responses against intestinal bacterial infections that elicit overlapping starvation and infection responses, the regulation of which is not well understood. Direct comparison of C. elegans that were starved or infected with Staphylococcus aureus revealed a large infection-specific transcriptional signature, which was almost completely abrogated by deletion of transcription factor hlh-30/TFEB, except for six genes including a flavin-containing monooxygenase (FMO) gene, fmo-2/FMO5. Deletion of fmo-2/FMO5 severely compromised infection survival, thus identifying the first FMO with innate immunity functions in animals. Moreover, fmo-2/FMO5 induction required the nuclear hormone receptor, NHR-49/PPAR-α, which controlled host defense cell non-autonomously. These findings reveal an infection-specific host response to S. aureus, identify HLH-30/TFEB as its main regulator, reveal FMOs as important innate immunity effectors in animals, and identify the mechanism of FMO regulation through NHR-49/PPAR-α during S. aureus infection, with implications for host defense and inflammation in higher organisms.

Amoxicilin and Clavulanic Acid Intercaled Nanostructures for Dentistry Uses

2019 ◽  
Vol 56 (2) ◽  
pp. 396-398
Author(s):  
Georgeta Zegan ◽  
Daniela Anistoroaei ◽  
Elena Mihaela Carausu ◽  
Eduard Radu Cernei ◽  
loredana Golovcencu
Keyword(s):  
Drug Delivery ◽  
Clavulanic Acid ◽  
Bacterial Infections ◽  
Drug Delivery Systems ◽  
Intracellular Transport ◽  
Oral Treatment ◽  
Chitosan Nanoparticles ◽  
Well Being ◽  
Cell Penetrating ◽  
Novel Drug

Amoxicillin and clavulanic acid are two of the most commonly prescribed antibacterial worldwide for treating oral infectious diseases. Oral health is of big importance for well-being and general health. A few novel drug delivery systems were designed for oral treatment and prophylaxis of different diseases in the oral cavity. This work focused on the latest drug delivery development of the most common oral pathologies, namely, periodontitis, oral mucosal infections, dental caries and oral cancer. Herein we reveal the synthesis, characterization and application of chitosan nanoparticles for intracellular transport of the weakly cell-penetrating amoxicillin and clavulanic acid in order to improve their efficacy on bacterial infections.

scholarly journals Immunological Aspects Related to Viral Infections in Severe Asthma and the Role of Omalizumab

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 348
Author(s):  
Francesco Menzella ◽  
Giulia Ghidoni ◽  
Carla Galeone ◽  
Silvia Capobelli ◽  
Chiara Scelfo ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Severe Asthma ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Antiviral Effect ◽  
Point Of View ◽  
Type I ◽  
Effector Cells ◽  
Viral Spread ◽  
Increased Risk

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although extremely limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which can stabilize the effector cells, and is becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allow a great improvement in the management of asthma.

scholarly journals Innate Immunity in Children and the Role of ACE2 Expression in SARS-CoV-2 Infection

2021 ◽  
Vol 13 (3) ◽  
pp. 363-382
Author(s):  
Mario Dioguardi ◽  
Angela Pia Cazzolla ◽  
Claudia Arena ◽  
Diego Sovereto ◽  
Giorgia Apollonia Caloro ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Viral Disease ◽  
Receptor Expression ◽  
Virus Infections ◽  
Search Terms ◽  
Bibliographic Search ◽  
Meta Analyses

COVID-19 (Coronavirus Disease 2019) is an emerging viral disease caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which leads to severe respiratory infections in humans. The first reports came in December 2019 from the city of Wuhan in the province of Hubei in China. It was immediately clear that children developed a milder disease than adults. The reasons for the milder course of the disease were attributed to several factors: innate immunity, difference in ACE2 (angiotensin-converting enzyme II) receptor expression, and previous infections with other common coronaviruses (CovH). This literature review aims to summarize aspects of innate immunity by focusing on the role of ACE2 expression and viral infections in children in modulating the antibody response to SARS-CoV-2 infection. This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles deemed potentially eligible were considered, including those dealing with COVID-19 in children and providing more up-to-date and significant data in terms of epidemiology, prognosis, course, and symptoms, focusing on the etiopathogenesis of SARS-CoV-2 disease in children. The bibliographic search was conducted using the search engines PubMed and Scopus. The following search terms were entered in PubMed and Scopus: COVID-19 AND ACE2 AND Children; COVID-19 AND Immunity innate AND children. The search identified 857 records, and 18 studies were applicable based on inclusion and exclusion criteria that addressed the issues of COVID-19 concerning the role of ACE2 expression in children. The scientific literature agrees that children develop milder COVID-19 disease than adults. Milder symptomatology could be attributed to innate immunity or previous CovH virus infections, while it is not yet fully understood how the differential expression of ACE2 in children could contribute to milder disease.

scholarly journals The Fungal Effector Avr-Pita Suppresses Innate Immunity by Increasing COX Activity in Rice Mitochondria

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jingluan Han ◽  
Xiaoyu Wang ◽  
Fengpin Wang ◽  
Zhe Zhao ◽  
Gousi Li ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Host Plant ◽  
Fungal Pathogen ◽  
Defense Responses ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Molecular Pattern ◽  
Ros Accumulation ◽  
Ros Metabolism ◽  
Increased Susceptibility

Abstract Background Avr-Pita was the first effector identified in the blast fungus (Magnaporthe oryzae)–rice (Oryza sativa) pathosystem. However, the molecular mechanism underlying its effects on the host plant has remained a long-standing mystery. Results Here, we report that ectopically expressing Avr-Pita in rice enhances susceptibility to M. oryzae and suppresses pathogen-associated molecular pattern (PAMP)-triggered defense responses. Avr-Pita targets the host mitochondria and interacts with the cytochrome c oxidase (COX) assembly protein OsCOX11, a key regulator of mitochondrial reactive oxygen species (ROS) metabolism in rice. Overexpressing Avr-Pita or OsCOX11 increased COX activity and decreased ROS accumulation triggered by the fungal PAMP chitin. OsCOX11-overexpressing plants showed increased susceptibility to M. oryzae, whereas OsCOX11-knockdown plants showed resistance to M. oryzae. Conclusions Taken together, these findings suggest that the fungal pathogen M. oryzae delivers the effector Avr-Pita to the host plant, where it enhances COX activity thus decreasing ROS accumulation. Therefore, this effector suppresses host innate immunity by perturbing ROS metabolism in the mitochondria.

scholarly journals A multicenter evaluation of viral bloodstream detections in children presenting to the Emergency Department with suspected systemic infection

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Christina A. Rostad ◽  
Neena Kanwar ◽  
Jumi Yi ◽  
Claudia R. Morris ◽  
Jennifer Dien Bard ◽  
...  
Keyword(s):  
Emergency Department ◽  
Whole Blood ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Systemic Infection ◽  
Common Symptom ◽  
Predictive Values ◽  
Healthcare Facilities ◽  
Tract Infections ◽  
Systemic Infections

Abstract Background Fever is a common symptom in children presenting to the Emergency Department (ED). We aimed to describe the epidemiology of systemic viral infections and their predictive values for excluding serious bacterial infections (SBIs), including bacteremia, meningitis and urinary tract infections (UTIs) in children presenting to the ED with suspected systemic infections. Methods We enrolled children who presented to the ED with suspected systemic infections who had blood cultures obtained at seven healthcare facilities. Whole blood specimens were analyzed by an experimental multiplexed PCR test for 7 viruses. Demographic and laboratory results were abstracted. Results Of the 1114 subjects enrolled, 245 viruses were detected in 224 (20.1%) subjects. Bacteremia, meningitis and UTI frequency in viral bloodstream-positive patients was 1.3, 0 and 10.1% compared to 2.9, 1.3 and 9.7% in viral bloodstream-negative patients respectively. Although viral bloodstream detections had a high negative predictive value for bacteremia or meningitis (NPV = 98.7%), the frequency of UTIs among these subjects remained appreciable (9/89, 10.1%) (NPV = 89.9%). Screening urinalyses were positive for leukocyte esterase in 8/9 (88.9%) of these subjects, improving the ability to distinguish UTI. Conclusions Viral bloodstream detections were common in children presenting to the ED with suspected systemic infections. Although overall frequencies of SBIs among subjects with and without viral bloodstream detections did not differ significantly, combining whole blood viral testing with urinalysis provided high NPV for excluding SBI.

scholarly journals The Antiviral Properties of Cyclosporine. Focus on Coronavirus, Hepatitis C Virus, Influenza Virus, and Human Immunodeficiency Virus Infections

Biology ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 192 ◽  
Author(s):  
Paulina Glowacka ◽  
Lidia Rudnicka ◽  
Olga Warszawik-Hendzel ◽  
Mariusz Sikora ◽  
Mohamad Goldust ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Influenza Virus ◽  
Hepatitis C ◽  
Beneficial Effect ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Skin Diseases ◽  
Current Knowledge ◽  
Immunosuppressive Treatment ◽  
Immunodeficiency Virus

This review updates current knowledge regarding the risk of viral infections, including COVID-19, in patients treated with cyclosporine. We also shortly refer to bacterial infections and parasitic infestations in patients treated with cyclosporin. Cyclosporine is an immunosuppressive drug, which is widely used in medicine, including in the treatment of autoimmune skin diseases in dermatology, rheumatology, ophthalmology and nephrology, and in organ transplantation. A usual concern associated with immunosuppressive treatment is the potential risk of infections. Interestingly, several data indicate a relatively low risk of infections, especially viral infections, in patients receiving cyclosporine. It was shown that cyclosporine exerts an inhibitory effect on the replication of some viruses, or may have a potentially beneficial effect on the disease course in infections. These include hepatitis C, influenza virus, rotavirus, human immunodeficiency virus and coronavirus infections. Available data indicate that cyclosporine may have a beneficial effect on COVID-19, which is caused by the coronavirus SARS-COV2.

scholarly journals Diagnostic performance of four SARS-CoV-2 antibody assays in patients with COVID-19 or with bacterial and non-SARS-CoV-2 viral respiratory infections

2021 ◽  
Author(s):  
Timo Huber ◽  
Philipp Steininger ◽  
Pascal Irrgang ◽  
Klaus Korn ◽  
Matthias Tenbusch ◽  
...  
Keyword(s):  
Legionella Pneumophila ◽  
False Positive ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Chlamydia Psittaci ◽  
Specific Flow ◽  
Antibody Assays ◽  
Positive Results ◽  
Viral Respiratory

AbstractSARS-CoV-2 antibody assays are used for epidemiological studies and for the assessment of vaccine responses in highly vulnerable patients. So far, data on cross-reactivity of SARS-CoV-2 antibody assays is limited. Here, we compared four enzyme-linked immunosorbent assays (ELISAs; Vircell SARS-CoV-2 IgM/IgA and IgG, Euroimmun SARS-CoV-2 IgA and IgG) for detection of anti-SARS-CoV-2 antibodies in 207 patients with COVID-19, 178 patients with serological evidence of different bacterial infections, 107 patients with confirmed viral respiratory disease, and 80 controls from the pre-COVID-19 era. In COVID-19 patients, the assays showed highest sensitivity in week 3 (Vircell-IgM/A and Euroimmun-IgA: 78.9% each) and after week 7 (Vircell-IgG: 97.9%; Euroimmun-IgG: 92.1%). The antibody indices were higher in patients with fatal disease. In general, IgM/IgA assays had only limited or no benefit over IgG assays. In patients with non-SARS-CoV-2 respiratory infections, IgG assays were more specific than IgM/IgA assays, and bacterial infections were associated with more false-positive results than viral infections. The specificities in bacterial and viral infections were 68.0 and 81.3% (Vircell-IgM/IgA), 84.8 and 96.3% (Euroimmun-IgA), 97.8 and 86.0% (Vircell-IgG), and 97.8 and 99.1% (Euroimmun-IgG), respectively. Sera from patients positive for antibodies against Mycoplasma pneumoniae, Chlamydia psittaci, and Legionella pneumophila yielded particularly high rates of unspecific false-positive results in the IgM/IgA assays, which was revealed by applying a highly specific flow-cytometric assay using HEK 293 T cells expressing the SARS-CoV-2 spike protein. Positive results obtained with anti-SARS-CoV-2 IgM/IgA ELISAs require careful interpretation, especially if there is evidence for prior bacterial respiratory infections.

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