Neutrophil in Reverse Migration: Role in Sepsis

Frontiers in Immunology ◽

10.3389/fimmu.2021.656039 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jingjing Ji ◽

Jie Fan

Keyword(s):

Host Response ◽

Immune Reaction ◽

Innate Immune ◽

Polymorphonuclear Neutrophils ◽

Current Evidence ◽

Protective Response ◽

Reverse Migration ◽

Inflammatory Site ◽

Life Threatening

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. During the development and progression of sepsis, polymorphonuclear neutrophils (PMNs) are the most abundantly recruited innate immune cells at sites of infection, playing critical roles in the elimination of local infection and healing of the injury. PMN reverse migration (rM) describes the phenomenon in which PMNs migrate away from the inflammatory site back into the vasculature following the initial PMN infiltration. The functional role of PMN rM within inflammatory scenarios requires further exploration. Current evidence suggests that depending on the context, PMN rM can be both a protective response, by facilitating an efficient resolution to innate immune reaction, and also a tissue-damaging event. In this review, we provide an overview of current advancements in understanding the mechanism and roles of PMN rM in inflammation and sepsis. A comprehensive understanding of PMN rM may allow for the development of novel prophylactic and therapeutic strategies for sepsis.

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Therapeutic Role of Tocilizumab in SARS-CoV-2-Induced Cytokine Storm: Rationale and Current Evidence

International Journal of Molecular Sciences ◽

10.3390/ijms22063059 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3059

Author(s):

Corrado Pelaia ◽

Cecilia Calabrese ◽

Eugenio Garofalo ◽

Andrea Bruni ◽

Alessandro Vatrella ◽

...

Keyword(s):

Review Article ◽

Lung Damage ◽

Current Evidence ◽

Therapeutic Effects ◽

Cytokine Storm ◽

Future Perspectives ◽

Pathogenic Role ◽

Refractory Rheumatoid Arthritis ◽

Life Threatening

Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab’s therapeutic effects in patients with life-threatening SARS-CoV-2 infection.

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CD69 Deficiency Enhances the Host Response to Vaccinia Virus Infection through Altered NK Cell Homeostasis

Journal of Virology ◽

10.1128/jvi.00550-16 ◽

2016 ◽

Vol 90 (14) ◽

pp. 6464-6474 ◽

Cited By ~ 7

Author(s):

Laura Notario ◽

Elisenda Alari-Pahissa ◽

Antonio de Molina ◽

Pilar Lauzurica

Keyword(s):

Immune Response ◽

Infection Control ◽

Vaccinia Virus ◽

Nk Cells ◽

Natural Killer ◽

Host Response ◽

Nk Cell ◽

Innate Immune ◽

Cell Numbers

ABSTRACTDuring the host response to viral infection, the transmembrane CD69 protein is highly upregulated in all immune cells. We have studied the role of CD69 in the murine immune response to vaccinia virus (VACV) infection, and we report that the absence of CD69 enhances protection against VACV at both short and long times postinfection in immunocompetent and immunodeficient mice. Natural killer (NK) cells were implicated in the increased infection control, since the differences were greatly diminished when NK cells were depleted. This role of NK cells was not based on an altered NK cell reactivity, since CD69 did not affect the NK cell activation threshold in response to major histocompatibility complex class I NK cell targets or protein kinase C activation. Instead, NK cell numbers were increased in the spleen and peritoneum of CD69-deficient infected mice. That was not just secondary to better infection control in CD69-deficient mice, since NK cell numbers in the spleens and the blood of uninfected CD69−/−mice were already augmented. CD69-deficient NK cells from infected mice did not have an altered proliferation capacity. However, a lower spontaneous cell death rate was observed for CD69−/−lymphocytes. Thus, our results suggest that CD69 limits the innate immune response to VACV infection at least in part through cell homeostatic survival.IMPORTANCEWe show that increased natural killer (NK) cell numbers augment the host response and survival after infection with vaccinia virus. This phenotype is found in the absence of CD69 in immunocompetent and immunodeficient hosts. As part of the innate immune system, NK lymphocytes are activated and participate in the defense against infection. Several studies have focused on the contribution of NK cells to protection against infection with vaccinia virus. In this study, it was demonstrated that the augmented early NK cell response in the absence of CD69 is responsible for the increased protection seen during infection with vaccinia virus even at late times of infection. This work indicates that the CD69 molecule may be a target of therapy to augment the response to poxvirus infection.

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Role of reactive intermediates in the immunopathogenesis of the pristane-induced Balb/c model of lupus

Lupus ◽

10.1177/0961203311418791 ◽

2011 ◽

Vol 20 (13) ◽

pp. 1421-1425 ◽

Cited By ~ 13

Author(s):

U Minhas ◽

P Das ◽

A Bhatnagar

Keyword(s):

Lupus Erythematosus ◽

Immune Reaction ◽

Reactive Intermediates ◽

Peritoneal Macrophages ◽

Innate Immune ◽

Antioxidant Defences ◽

Single Intraperitoneal Injection ◽

New Findings ◽

Autoimmune Condition

Pristane-induced lupus in Balb/c mice represents an environmentally induced lupus model which is widely used for unravelling the mystery of the pathogenesis of the disease. An intraperitoneal innate immune reaction to pristane is primarily accountable for the development of the systemic lupus erythematosus-like disease in the model. In this study, reactive oxygen species (ROS) and nitric oxide (NO) levels were assessed (as a measure of chronic inflammation) in the peritoneum of the Balb/c model of SLE-like disease 6 months after a single intraperitoneal injection of pristane. Levels of ROS in peritoneal macrophages were significantly enhanced (mean fluorescence value ± SD: 648 ± 100.9) in pristane-treated mice (PT) as compared with control mice (mean fluorescence value ± SD: 79 ± 7.8) treated with phosphate buffer saline (PBST). An immunofluorescence study reveal the localization of ROS within nuclei, suggesting oxidative damage. Similarly, levels of NO were also markedly raised in PT mice (34.71 µmol/l ± 8.48) as compared with PBST mice (1.36 nmol/l ± 0.14). These new findings lead to speculation about the role of reactive intermediates in the development of disease. This study proposes that the sustained production of reactive intermediates during chronic intraperitoneal inflammation might reduce antioxidant defences and lead to a condition of oxidative stress, which might further be responsible for this autoimmune condition.

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Iron metabolism in trypanosomatids, and its crucial role in infection

Parasitology ◽

10.1017/s0031182009991880 ◽

2010 ◽

Vol 137 (6) ◽

pp. 899-917 ◽

Cited By ~ 50

Author(s):

M. C. TAYLOR ◽

J. M. KELLY

Keyword(s):

Iron Metabolism ◽

Iron Uptake ◽

Host Response ◽

Alternative Oxidase ◽

Protective Response ◽

Antioxidant Defence ◽

African Trypanosomes ◽

Zip Family ◽

Living Organisms

SUMMARYIron is almost ubiquitous in living organisms due to the utility of its redox chemistry. It is also dangerous as it can catalyse the formation of reactive free radicals – a classical double-edged sword. In this review, we examine the uptake and usage of iron by trypanosomatids and discuss how modulation of host iron metabolism plays an important role in the protective response. Trypanosomatids require iron for crucial processes including DNA replication, antioxidant defence, mitochondrial respiration, synthesis of the modified base J and, in African trypanosomes, the alternative oxidase. The source of iron varies between species. Bloodstream-form African trypanosomes acquire iron from their host by uptake of transferrin, andLeishmania amazonensisexpresses a ZIP family cation transporter in the plasma membrane. In other trypanosomatids, iron uptake has been poorly characterized. Iron-withholding responses by the host can be a major determinant of disease outcome. Their role in trypanosomatid infections is becoming apparent. For example, the cytosolic sequestration properties of NRAMP1, confer resistance against leishmaniasis. Conversely, cytoplasmic sequestration of iron may be favourable rather than detrimental toTrypanosoma cruzi. The central role of iron in both parasite metabolism and the host response is attracting interest as a possible point of therapeutic intervention.

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Role of Specialized Pro-Resolving Mediators in Modifying Host Defense and Decreasing Bacterial Virulence

Molecules ◽

10.3390/molecules26226970 ◽

2021 ◽

Vol 26 (22) ◽

pp. 6970

Author(s):

Julianne M. Thornton ◽

Kingsley Yin

Keyword(s):

Host Defense ◽

Host Response ◽

Tissue Repair ◽

Defense Mechanisms ◽

Neutrophil Migration ◽

Bacterial Virulence ◽

Innate Immune ◽

Bioactive Fatty Acids ◽

Insight Into

Bacterial infection activates the innate immune system as part of the host’s defense against invading pathogens. Host response to bacterial pathogens includes leukocyte activation, inflammatory mediator release, phagocytosis, and killing of bacteria. An appropriate host response requires resolution. The resolution phase involves attenuation of neutrophil migration, neutrophil apoptosis, macrophage recruitment, increased phagocytosis, efferocytosis of apoptotic neutrophils, and tissue repair. Specialized Pro-resolving Mediators (SPMs) are bioactive fatty acids that were shown to be highly effective in promoting resolution of infectious inflammation and survival in several models of infection. In this review, we provide insight into the role of SPMs in active host defense mechanisms for bacterial clearance including a new mechanism of action in which an SPM acts directly to reduce bacterial virulence.

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Involvement of Mitochondrial Disorders in Septic Cardiomyopathy

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/4076348 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 16

Author(s):

Arthur Durand ◽

Thibault Duburcq ◽

Thibault Dekeyser ◽

Remi Neviere ◽

Michael Howsam ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Cardiac Dysfunction ◽

Host Response ◽

Therapeutic Strategies ◽

Future Research ◽

Septic Cardiomyopathy ◽

Research Directions ◽

Life Threatening ◽

Future Research Directions

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It remains a leading cause of death worldwide, despite the development of various therapeutic strategies. Cardiac dysfunction, also referred to as septic cardiomyopathy, is a frequent and well-described complication of sepsis and associated with worse clinical outcomes. Recent research has increased our understanding of the role of mitochondrial dysfunction in the pathophysiology of septic cardiomyopathy. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions.

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The Relevance of Coding Gene Polymorphysms of Cytokines and Cellular Receptors in Sepsis

The Journal of Critical Care Medicine ◽

10.1515/jccm-2017-0001 ◽

2017 ◽

Vol 3 (1) ◽

pp. 5-11 ◽

Cited By ~ 2

Author(s):

Anca Meda Georgescu ◽

Bianca Liana Grigorescu ◽

Ioana Raluca Chirteș ◽

Alexander A. Vitin ◽

Raluca Ștefania Fodor

Keyword(s):

Septic Shock ◽

Genetic Variation ◽

Host Response ◽

Serum Proteins ◽

Research Topic ◽

Current Evidence ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Cellular Receptors

AbstractSepsis is an injurious systemic host response to infection, which can often lead to septic shock and death. Recently, the immune-pathogenesis and genomics of sepsis have become a research topic focusing on the establishment of diagnostic and prognostic biomarkers. As yet, none have been identified as having the necessary specificity to be used independently of other factors in this respect. However the accumulation of current evidence regarding genetic variations, especially the single nucleotide polymorphisms (SNPs) of cytokines and other innate immunity determinants, partially explains the susceptibility and individual differences of patients with regard to the evolution of sepsis. This article outlines the role of genetic variation of some serum proteins which have the potential to be used as biomarker values in evaluating sepsis susceptibility and the progression of the condition.

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Role of Lopinavir/Ritonavir in the Treatment of Covid-19: A Review of Current Evidence, Guideline Recommendations, and Perspectives

Journal of Clinical Medicine ◽

10.3390/jcm9072050 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2050 ◽

Cited By ~ 6

Author(s):

Simone Meini ◽

Alberto Pagotto ◽

Benedetta Longo ◽

Igor Vendramin ◽

Davide Pecori ◽

...

Keyword(s):

Clinical Trial ◽

Respiratory Illness ◽

Organ Damage ◽

Current Evidence ◽

Laboratory Studies ◽

Scientific Societies ◽

Pathogenetic Role ◽

Proven Efficacy ◽

Life Threatening

A life-threatening respiratory illness (COVID-19) due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus was first described in December 2019 in Wuhan (China), rapidly evolving into a pandemic. In the first phase, when the viral replication plays a pivotal pathogenetic role, antiviral drugs could be crucial in limiting viral-induced organ damage. Unfortunately, there are no specific antivirals of proven efficacy for COVID-19, and several drugs have been repurposed to face this dramatic pandemic. In this paper we review the studies evaluating lopinavir/ritonavir association (LPV/r) use in COVID-19, and previously in SARS and Middle East respiratory syndrome (MERS). We searched PubMed to identify all relevant clinical and laboratory studies published up to 15 May 2020; the guidelines on the use of LPV/r in COVID-19 were further directly searched on the website of the main international scientific societies and agencies. Available evidence is currently scarce and of low quality. The recommendations issued for COVID-19 vary from positions clearly against the use of LPV/r to other positions that are more favorable. In our opinion, despite the controversial results of an important randomized clinical trial, and some recommendations, clinicians should not abandon the use of LPV/r for the treatment of COVID-19, possibly using this drug inside a prospective randomized trial, waiting for the results of the numerous ongoing trials evaluating its efficacy.

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Interferon and Toll-Like Receptor 7 Response in COVID-19: Implications of Topical Imiquimod for Prophylaxis and Treatment

Dermatology ◽

10.1159/000518471 ◽

2021 ◽

pp. 1-10

Author(s):

Mindy D. Szeto ◽

Jalal Maghfour ◽

Torunn E. Sivesind ◽

Jarett Anderson ◽

Jadesola T. Olayinka ◽

...

Keyword(s):

Immune System ◽

Innate Immune System ◽

Critical Role ◽

Innate Immune ◽

Current Evidence ◽

Loss Of Function ◽

Strong Immune Response ◽

Topical Imiquimod ◽

Pubmed Database

Background: The innate immune system is recognized as an essential aspect of COVID-19 pathogenesis. Toll-like receptors (TLRs) are important in inducing antiviral response, triggering downstream production of interferons (IFNs). Certain loss-of-function variants in TLR7 are associated with increased COVID-19 disease severity, and imiquimod (ImiQ) is known to have immunomodulating effects as an agonist of TLR7. Given that topical imiquimod (topImiQ) is indicated for various dermatologic conditions, it is necessary for dermatologists to understand the interplay between innate immunity mechanisms and the potential role of ImiQ in COVID-19, with a particular focus on TLR7. Summary: Our objective was to survey recent peer-reviewed scientific literature in the PubMed database, examine relevant evidence, and elucidate the relationships between IFNs, TLR7, the innate immune system, and topImiQ in the context of COVID-19. Despite limited studies on this topic, current evidence supports the critical role of TLRs in mounting a strong immune response against COVID-19. Of particular interest to dermatologists, topImiQ can result in systemic upregulation of the immune system via activation of TLR7. Key Message: Given the role of TLR7 in the systemic activation of the immune system, ImiQ, as a ligand of the TLR7 receptor, may have potential therapeutic benefit as a topical immunomodulatory treatment for COVID-19.

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