scholarly journals Hyperinflammation Syndrome in COVID-19 Disease: Pathogenesis and Potential Immunomodulatory Agents

2021 ◽  
Author(s):  
Moulid Hidayat ◽  
Diah Handayani ◽  
Fariz Nurwidya ◽  
Sita Laksmi Andarini
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Distress Syndrome ◽  
Multiorgan Failure ◽  
Immunosuppressive Agents ◽  
Clinical Manifestations ◽  
Disease Pathogenesis ◽  
Immunomodulatory Agents ◽  
Host Immune Responses ◽  
The World

The coronavirus disease 2019 (COVID-19) pandemic caused by infection of the SARS-CoV-2 virus has affected millions of people in the world. The pathogenesis and clinical manifestations of COVID-19 disease are tightly influenced by the host immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. In some condition, the immune response might be uncontrolled, giving rise to hyperinflammatory conditions marked by excessive release of proinflammatory cytokines (cytokine storms) in severe COVID-19 patients, which then can cause acute respiratory distress syndrome (ARDS), multiorgan failure, and death. Furthermore, treatment using immunomodulator agents including immunostimulatory and immunosuppressive agents can be an option in achieving successful treatment. In this review, we discuss the pathogenesis of the disease, including host immune responses to SARS-CoV-2 virus infection, and immune mechanisms which contribute to the disease severity and death as well as several potential immunomodulatory agents which can be used in the management of hyperinflammatory syndrome of severe COVID-19.

scholarly journals Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 629
Author(s):  
Megan M. Dunagan ◽  
Kala Hardy ◽  
Toru Takimoto
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Populations ◽  
Lymphocyte Migration ◽  
Host Immune Responses ◽  
Mhc Molecules ◽  
The Impact

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.

scholarly journals Extracellular Vesicles from Different Pneumococcal Serotypes Are Internalized by Macrophages and Induce Host Immune Responses

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1530
Author(s):  
Alfonso Olaya-Abril ◽  
Rafael Prados-Rosales ◽  
José A. González-Reyes ◽  
Arturo Casadevall ◽  
Liise-anne Pirofski ◽  
...  
Keyword(s):  
Immune Response ◽  
Biological Activity ◽  
Immune Responses ◽  
Extracellular Vesicles ◽  
Host Cells ◽  
Pneumococcal Serotypes ◽  
Human Pathogen ◽  
Host Immune Responses ◽  
Serotype 1 ◽  
Transient Loss

Bacterial extracellular vesicles are membranous ultrastructures released from the cell surface. They play important roles in the interaction between the host and the bacteria. In this work, we show how extracellular vesicles produced by four different serotypes of the important human pathogen, Streptococcus pneumoniae, are internalized by murine J774A.1 macrophages via fusion with the membrane of the host cells. We also evaluated the capacity of pneumococcal extracellular vesicles to elicit an immune response by macrophages. Macrophages treated with the vesicles underwent a serotype-dependent transient loss of viability, which was further reverted. The vesicles induced the production of proinflammatory cytokines, which was higher for serotype 1 and serotype 8-derived vesicles. These results demonstrate the biological activity of extracellular vesicles of clinically important pneumococcal serotypes.

scholarly journals How to Control Covid-19 with a Nanobiotherapy?

2020 ◽  
Keyword(s):  
Intensive Care Unit ◽  
Immune Response ◽  
Acute Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Multiple Organ ◽  
World Health ◽  
Shortness Of Breath ◽  
The World ◽  
Health Organization ◽  
Muscle Ache

The outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China has been brought to global attention and declared a pandemic by the World Health Organization (WHO) on March 11, 2020. In a recent study of Nanshan Chen et al., on patients of Wuhan Jinyintan Hospital, Wuhan, China, from the 99 patients with SARSCoV-2 infection, 51% had chronic diseases and they had symptoms of fever (83%), cough (82%) shortness of breath (31%), muscle ache (11%), fatigue (9%), headache (8%), sore throat (5%), rhinorrhea (4%), chest pain (2%), diarrhea (2%), and nausea and vomiting (1%) [1, 2]. The majority of patients can recover, however, about 25% of patients will progress into severe complications including acute respiratory distress syndrome (ARDS), which may worsen rapidly into respiratory failure, need an intensive care unit (ICU) and even cause multiple organ failure [3]. Depending on the pathophysiological mechanisms supposed to be involved in the development of the various clinical forms of the disease, various types of treatment have been tested with varying degrees of success. We have developed a nanotherapy to block the entry of the virus into the host cell, to reduce its potential for replication and to regulate the immune response against the microbial aggressor [4].

scholarly journals Protective and Pathogenic Immune Responses to Cutaneous Leishmaniasis

2021 ◽  
Author(s):  
Elina Panahi ◽  
Danielle I. Stanisic ◽  
Christopher S. Peacock ◽  
Lara J. Herrero
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Cutaneous Leishmaniasis ◽  
Adaptive Immune Response ◽  
Leishmania Parasite ◽  
Host Immune System ◽  
Phagocytic Cells ◽  
Host Immune Responses ◽  
Outcome Severity ◽  
Common Clinical Presentation

Leishmania (Kinetoplastida: Trypanosomatidae) parasites are known to cause a broad spectrum of clinical diseases in humans, collectively known as the leishmaniases. Cutaneous leishmaniasis is the most common clinical presentation with varying degrees of severity largely driven by host immune responses, specifically the interplay between innate and adaptive immune response. The establishment of a T lymphocyte driven cell-mediated immune response, leading to activated phagocytic cells, leading to Leishmania parasite killing and control of infection. Alternatively, the Leishmania parasite manipulates the host immune system, enabling parasite proliferation and clinical disease. Here we review how the cumulative interactions of different aspects of the host immune response determines disease outcome, severity, and immunity to re-infection.

scholarly journals Multiomic Immunophenotyping of COVID-19 Patients Reveals Early Infection Trajectories

2020 ◽  
Author(s):  
Yapeng Su ◽  
Daniel Chen ◽  
Christopher Lausted ◽  
Dan Yuan ◽  
Jongchan Choi ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Surface Proteins ◽  
Host Immune Responses ◽  
Therapeutic Development ◽  
Clinical Measures ◽  
Whole Transcriptome

SUMMARYHost immune responses play central roles in controlling SARS-CoV2 infection, yet remain incompletely characterized and understood. Here, we present a comprehensive immune response map spanning 454 proteins and 847 metabolites in plasma integrated with single-cell multi-omic assays of PBMCs in which whole transcriptome, 192 surface proteins, and T and B cell receptor sequence were co-analyzed within the context of clinical measures from 50 COVID19 patient samples. Our study reveals novel cellular subpopulations, such as proliferative exhausted CD8+ and CD4+ T cells, and cytotoxic CD4+ T cells, that may be features of severe COVID-19 infection. We condensed over 1 million immune features into a single immune response axis that independently aligns with many clinical features and is also strongly associated with disease severity. Our study represents an important resource towards understanding the heterogeneous immune responses of COVID-19 patients and may provide key information for informing therapeutic development.

scholarly journals Host Immune Response and Novel Diagnostic Approach to NTM Infections

2020 ◽  
Vol 21 (12) ◽  
pp. 4351
Author(s):  
Yuko Abe ◽  
Kiyoharu Fukushima ◽  
Yuki Hosono ◽  
Yuki Matsumoto ◽  
Daisuke Motooka ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Humoral Immunity ◽  
Diagnostic Approach ◽  
Post Transplantation ◽  
Diagnosis And Management ◽  
Immunological Responses ◽  
Host Immune Responses ◽  
Diagnostic Approaches ◽  
Proper Diagnosis

The incidence and prevalence of non-tuberculous mycobacteria (NTM) infections are steadily increasing worldwide, partially due to the increased incidence of immunocompromised conditions, such as the post-transplantation state. The importance of proper diagnosis and management of NTM infection has been recently recognized. Host immunological responses play integral roles in vulnerability to NTM infections, and may contribute to the onset of specific types of NTM infection. Furthermore, distinct NTM species are known to affect and attenuate these host immune responses in unique manners. Therefore, host immune responses must be understood with respect to each causative NTM species. Here, we review innate, cellular-mediated, and humoral immunity to NTM and provide perspectives on novel diagnostic approaches regarding each NTM species.

scholarly journals Analysis of Tuberculosis Meningitis Pathogenesis, Diagnosis, and Treatment

2020 ◽  
Vol 9 (9) ◽  
pp. 2962
Author(s):  
Aysha Arshad ◽  
Sujay Dayal ◽  
Raj Gadhe ◽  
Ajinkya Mawley ◽  
Kevin Shin ◽  
...  
Keyword(s):  
Immune Responses ◽  
Initial Phase ◽  
Multidrug Resistant ◽  
Personality Change ◽  
Diagnosis And Treatment ◽  
Host Immune Responses ◽  
Common Presentation ◽  
Neurological Morbidity ◽  
The World ◽  
Resistant Strains

Tuberculosis (TB) is the most prevalent infectious disease in the world. In recent years there has been a significant increase in the incidence of TB due to the emergence of multidrug resistant strains of Mycobacterium tuberculosis (M. tuberculosis) and the increased numbers of highly susceptible immuno-compromised individuals. Central nervous system TB, includes TB meningitis (TBM-the most common presentation), intracranial tuberculomas, and spinal tuberculous arachnoiditis. Individuals with TBM have an initial phase of malaise, headache, fever, or personality change, followed by protracted headache, stroke, meningismus, vomiting, confusion, and focal neurologic findings in two to three weeks. If untreated, mental status deteriorates into stupor or coma. Delay in the treatment of TBM results in, either death or substantial neurological morbidity. This review provides latest developments in the biomedical research on TB meningitis mainly in the areas of host immune responses, pathogenesis, diagnosis, and treatment of this disease.

scholarly journals Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses

2016 ◽  
Vol 90 (8) ◽  
pp. 3810-3818 ◽  
Author(s):  
Bjoern Meyer ◽  
Hinh Ly
Keyword(s):  
Immune Responses ◽  
Immune Evasion ◽  
Molecular Mechanisms ◽  
Multiorgan Failure ◽  
Hemorrhagic Fever ◽  
Innate Immune ◽  
Lassa Virus ◽  
Immune Recognition ◽  
African Countries ◽  
Host Immune Responses

Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options.

scholarly journals Recent advances in understanding inherited deficiencies in immunity to infections

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 243 ◽  
Author(s):  
Gregory M. Constantine ◽  
Michail S. Lionakis
Keyword(s):  
Immune Responses ◽  
Host Defense ◽  
Fungal Infections ◽  
Microbial Pathogens ◽  
Host Immune Responses ◽  
Vaccination Strategies ◽  
The World ◽  
Human Immunity ◽  
Immune Pathways ◽  
Resistance To Infection

The immune system is central to our interactions with the world in which we live and importantly dictates our response to potential allergens, toxins, and pathogens to which we are constantly exposed. Understanding the mechanisms that underlie protective host immune responses against microbial pathogens is vital for the development of improved treatment and vaccination strategies against infections. To that end, inherited immunodeficiencies that manifest with susceptibility to bacterial, viral, and/or fungal infections have provided fundamental insights into the indispensable contribution of key immune pathways in host defense against various pathogens. In this mini-review, we summarize the findings from a series of recent publications in which inherited immunodeficiencies have helped illuminate the interplay of human immunity and resistance to infection.

scholarly journals Infection, Inflammation and Immunity in Covid-19 Infection

2021 ◽  
Vol 48 (3) ◽  
pp. 77-82
Author(s):  
R. Cherneva ◽  
Z. Cherneva
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Immune Responses ◽  
Systemic Inflammation ◽  
Multiple Organ ◽  
Host Immunity ◽  
Effective Prevention ◽  
Systemic Complications ◽  
Host Immune Responses ◽  
Prevention And Treatment

Abstract The COVID-19 pandemic caused by the SARS-CoV-2 has increased the burden on healthcare system. Despite some progress in its diagnostics has been made, effective prevention and treatment are still insufficient. Since SARS-CoV-2 infections often cause systemic inflammation and multiple organ failure, the therapeutic options aimed at modulating the host immune responses to prevent subsequent systemic complications are demanding. The review provides a summary of the SARS-CoV-2 virus infection and underlines the current perception of pulmonary host’s immune response and its contributions to disease severity and systemic inflammation. Signaling pathways which have the potential to manipulate host immunity and improve clinical outcomes are also presented.

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