Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis

AbstractThe objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.

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Leptin’s and antigen-presenting cells’ functions in periodontitis – an overview / Leptin e as funções das células que apresentam antigénios na periodontite - uma visão geral

Brazilian Journal of Health Review ◽

10.34119/bjhrv4n2-333 ◽

2021 ◽

Vol 4 (2) ◽

pp. 8011-8019

Author(s):

Giovanna Ganem Favero ◽

Isabela Lopes Martin ◽

Fernanda Pereira da Silva Albino ◽

Carlos Eduardo Fontana ◽

Sérgio Luiz Pinheiro ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Immune Responses ◽

Inflammatory Responses ◽

Antigen Presenting Cells ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Inflammatory Immune Response ◽

Antigen Presenting ◽

The Relationship

Leptin is a hormone synthesized predominantly by white adipose tissue. Its production levels are directly proportional to the total mass of this tissue in an individual’s body. Apart from its classic role in the regulation of hunger and satiety, it also plays an important part in scenarios involving innate and adaptive immune responses. It has been discovered that leptin levels are altered in a variety of inflammatory responses, such as periodontitis, a condition which derives from a persistent inflammatory immune response from a host facing bacterial infection. The initial trigger for this reaction is the recognition of the pathogens by antigen presenting cells, such as macrophages and dendritic cells, whose actions can be influenced by leptin. This review aims to present the relationship between leptin, dendritic cells and macrophages in the context of periodontal disease. Thus, we have assembled the most important findings related to leptin’s role in the modulation of the immune response carried out by these cells in periodontitis.

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Dual-Wavelength Photosensitive Nano-in-Micro Scaffold Regulates Innate and Adaptive Immune Responses for Osteogenesis

Nano-Micro Letters ◽

10.1007/s40820-020-00540-z ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Qin Zhao ◽

Miusi Shi ◽

Chengcheng Yin ◽

Zifan Zhao ◽

Jinglun Zhang ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Immune Cells ◽

Inflammatory Responses ◽

Macrophage Polarization ◽

T Cell Response ◽

Dual Wavelength ◽

M2 Macrophage ◽

Adaptive Immune Responses ◽

Adaptive Immune

AbstractThe immune response of a biomaterial determines its osteoinductive effect. Although the mechanisms by which some immune cells promote regeneration have been revealed, the biomaterial-induced immune response is a dynamic process involving multiple cells. Currently, it is challenging to accurately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials. Herein, we investigated the roles of macrophages and dendritic cells (DCs) during the osteoinduction of biphasic calcium phosphate (BCP) scaffolds. We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation, resulting in low T cell response and efficient osteogenesis. Accordingly, a dual-targeting nano-in-micro scaffold (BCP loaded with gold nanocage, BCP-GNC) was designed to regulate the immune responses of macrophages and DCs. Through a dual-wavelength photosensitive switch, BCP-GNC releases interleukin-4 in the early stage of osteoinduction to target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs, creating a desirable inflammatory environment for osteogenesis. This study demonstrates that biomaterials developed to have specific regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis.

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Comparison of the Immunogenicities and Cross-Lineage Efficacies of Live Attenuated Peste des Petits Ruminants Virus Vaccines PPRV/Nigeria/75/1 and PPRV/Sungri/96

Journal of Virology ◽

10.1128/jvi.01471-18 ◽

2018 ◽

Vol 92 (24) ◽

Cited By ~ 12

Author(s):

Sophia Hodgson ◽

Katy Moffat ◽

Holly Hill ◽

John T. Flannery ◽

Simon P. Graham ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Immune Responses ◽

Severe Disease ◽

Small Ruminants ◽

Virus Antigen ◽

Enzyme Linked Immunosorbent Assay ◽

Peste Des Petits Ruminants ◽

Systematic Analysis ◽

Genetic Lineages

ABSTRACTPeste des petits ruminants (PPR) is a severe disease of goats and sheep that is widespread in Africa, the Middle East, and Asia. Several effective vaccines exist for the disease, based on attenuated strains of the virus (PPRV) that causes PPR. While the efficacy of these vaccines has been established by use in the field, the nature of the protective immune response has not been determined. In addition, while the vaccine derived from PPRV/Nigeria/75/1 (N75) is used in many countries, those developed in India have never been tested for their efficacy outside that country. We have studied the immune response in goats to vaccination with either N75 or the main Indian vaccine, which is based on isolate PPRV/India/Sungri/96 (S96). In addition, we compared the ability of these two vaccines, in parallel, to protect animals against challenge with pathogenic viruses from the four known genetic lineages of PPRV, representing viruses from different parts of Africa, as well as Asia. These studies showed that, while N75 elicited a stronger antibody response than S96, as measured by both enzyme-linked immunosorbent assay and virus neutralization, S96 resulted in more pronounced cellular immune responses, as measured by virus antigen-induced proliferation and interferon gamma production. While both vaccines induced comparable numbers of PPRV-specific CD8+T cells, S96 induced a higher number of CD4+T cells specifically responding to virus. Despite these quantitative and qualitative differences in the immune responses following vaccination, both vaccines gave complete clinical protection against challenge with all four lineages of PPRV.IMPORTANCEDespite the widespread use of live attenuated PPRV vaccines, this is the first systematic analysis of the immune response elicited in small ruminants. These data will help in the establishment of the immunological determinants of protection, an important step in the development of new vaccines, especially DIVA vaccines using alternative vaccination vectors. This study is also the first controlled test of the ability of the two major vaccines used against virulent PPRV strains from all genetic lineages of the virus, showing conclusively the complete cross-protective ability of these vaccines.

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Melanization of Cryptococcus neoformans Affects Lung Inflammatory Responses during Cryptococcal Infection

Infection and Immunity ◽

10.1128/iai.73.4.2012-2019.2005 ◽

2005 ◽

Vol 73 (4) ◽

pp. 2012-2019 ◽

Cited By ~ 54

Author(s):

Aron J. Mednick ◽

Joshua D. Nosanchuk ◽

Arturo Casadevall

Keyword(s):

Immune Response ◽

Immune Responses ◽

Cryptococcus Neoformans ◽

Inflammatory Responses ◽

Interleukin 4 ◽

Additional Mechanism ◽

Cryptococcal Infection ◽

Immunomodulatory Properties ◽

Oxidative Attack

ABSTRACT The production of melanin pigments is associated with virulence for many microbes. Melanin is believed to contribute to microbial virulence by protecting microbial cells from oxidative attack during infection. However, there is also evidence from various systems that melanins have immunomodulatory properties, which conceivably could contribute to virulence by altering immune responses. To investigate the effect of melanin on the immune response, we compared the murine pulmonary responses to infection with melanized and nonmelanized Cryptococcus neoformans cells. Infection with melanized cells resulted in a greater fungal burden during the early stages of infection and was associated with higher levels of interleukin-4 and MCP-1 and greater numbers of infiltrating leukocytes. Infection with laccase-positive (melanotic) C. neoformans cells also elicited higher MCP-1 levels and more infiltrating leukocytes than did infection with laccase-negative cells. Melanization interfered with phagocytosis in vivo for encapsulated C. neoformans but not for nonencapsulated cells. The results provide strong evidence that cryptococcal melanization can influence the immune response to infection and suggest that immunomodulation is an additional mechanism by which the pigment contributes to virulence.

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ANTIBODY RESPONSE TO COVID-19 INFECTION- CLINICAL VARIABLES AT PLAY

10.1101/2020.11.20.20234500 ◽

2020 ◽

Author(s):

Anuj Parkash ◽

Parul Singla ◽

Meenu Bhatia

Keyword(s):

Immune Response ◽

Immune Responses ◽

Disease Severity ◽

Statistical Significance ◽

Severe Disease ◽

Initial Symptom ◽

Igg Antibody ◽

Duration Of Symptoms ◽

Clinical Variables ◽

Significant Difference

ABSTRACTBackgroundThe current COVID19 pandemic began in December 2019 and rapidly expanded to become a global pandemic. The COVID 19 presents multitude of clinical disorders, ranges from asymptomatic infection to severe disease, which can accompanied by multisystem failure leading to death. The immune response to SARS CoV 2 is understood to involve all the components of the system that together causes viral elimination and recovery from the infection. However, such immune responses implicated in the disease has varied presentation ranging from mild to a severe form, which appears to hinge on the loss of the immune regulation between protective and altered responses. In this study, we want to unravel this association of immune responses to various clinical variables, which might have a major role to play, while generating the immune response. The objective was to test this hypothesis in our settings and comparing the results of serologic tests from a group of COVID 19 patients and will analyzed the disease severity in comparison.MethodsTesting for SARS COV2 IgG Antibody was done with chemiluminescent assay on the Ortho Clinical Diagnostic’s (OCD) Vitros 5600 platform.ResultsA total of 106 COVID 19 patients were included in this study, of whom 61 were male and 45 were female. Their mean age was 43.7 years (range 17–83) and the median interval between initial symptom onset and sample collection was 12.33 days. Eighty patients (82%) had mild or moderate symptoms and twenty-six patients (18%) had severe symptoms. The antibody titers were positive in 99 patients (93%) and were found negative in 7 patients (7%). When comparing patients with mild/moderate symptoms and patients with severe/critical diseases, no statistically significant difference was observed between their gender ratios (P = 0.373) and age composition (P = 0.224).ConclusionsThe data presented in this research study did not find any statistical significance between SARS CoV 2 IgG antibody levels with COVID 19 disease severity, duration of symptoms, age, gender, and length of convalescence.

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Host immune response to infection with porcine circoviruses

Animal Diseases ◽

10.1186/s44149-021-00027-3 ◽

2021 ◽

Vol 1 (1) ◽

Author(s):

Ruihan Shi ◽

Lei Hou ◽

Jue Liu

Keyword(s):

Immune Response ◽

Immune Responses ◽

Inflammatory Responses ◽

Porcine Circovirus Type ◽

Porcine Circovirus Type 2 ◽

Immune Defense ◽

Porcine Circovirus ◽

Future Research ◽

Host Immune System

AbstractPorcine circovirus type 2 (PCV2), which serves as a major causative agent of PCV2-associated diseases and causes severe loss to the pig industry worldwide, can dysregulate the immune response and induce immunosuppression in PCV2-infected pigs. Similar to PCV2, porcine circovirus type 3 (PCV3), a newly identified swine circovirus which might be closely associated with porcine dermatitis and nephropathy syndrome, reproductive disorder, and multisystemic inflammatory responses, also interferes with host immune defense. Interaction between host immune system and PCVs is considered to be a crucial determinant of pathogenicity in pigs. Here, we sought to briefly discuss the current knowledge regarding the interaction of porcine circovirus type 2 and/or 3 with host immune cells and immune responses to better depict the viral immunomodulatory capacity, pathogenic mechanisms, and the future research direction in host immune responses to infection with PCV2 and PCV3.

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Clustering Analysis of Splenocyte MicroRNAs in Pig Reveals the Key Signal Regulators in Immune Modulation of the Host During the Acute and Chronic Toxoplasma Gondii Infection

10.21203/rs.3.rs-1059248/v1 ◽

2021 ◽

Author(s):

Zhaofeng Hou ◽

Hui Zhang ◽

Kangzhi Xu ◽

Shifan Zhu ◽

Lele Wang ◽

...

Keyword(s):

Immune Response ◽

Toxoplasma Gondii ◽

Immune Responses ◽

Signaling Pathway ◽

Hierarchical Clustering ◽

Immune Regulation ◽

Clustering Analysis ◽

Expression Patterns ◽

Signaling Molecules ◽

Receptor Interaction

Abstract Background: Toxoplasma gondii is an obligatory intracellular protozoan parasite that can cause a geographically widespread zoonosis. Our previous splenocyte microRNA profiles analyses of pig infected with T. gondii revealed that the coordination of a large number of miRNAs regulates the host immune response during infection. However, the functions of more miRNAs involved to the immune regulation during T. gondii infection are not yet known.Methods: Clustering analysis was performed by K-means, self-organizing map (SOM) and Hierarchical clustering, respectively, to obtain miRNA groups with the similar expression patterns. Then, the target genes of miRNA group in each subcluster were further analyzed for function enrichment by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway to recognize the key signaling molecules and the regulatory signatures of the innate and adaptive immune responses of the host during T. gondii infection.Results: A total of 252 miRNAs were successfully divided into 22 subclusters by K-means clustering (named by K1~K22), 29 subclusters by SOM clustering (named by SOM1~SOM29) and 6 subclusters by Hierarchical clustering (named by H1~H6) based on their dynamic expression levels in the different infection stages. A total of 634, 660 and 477 GO terms, 15, 26 and 14 KEGG pathways, and 16, 15 and 7 Reactome pathways were significantly enriched by K-means, SOM and Hierarchical clustering, respectively. Of note, up to 22 miRNAs mainly showing the downregulated expression at 50 DPI were identified into one subcluster (namely subcluster H3-K17-SOM1) through the three algorithms. Functional analysis revealed that a large group of immunomodulatory signaling molecules were controlled by the different miRNA groups to regulate multiple immune processes, for instance, IL-1-mediated cellular response and Th1/Th2 cell differentiation partly depending on Notch signaling transduction for subclusters K1 and K2, innate immune response involving to Neutrophil degranulation and TLR4 cascade signaling for subcluster K15, B cell activation for subclusters SOM17, SOM1 and SOM25, leukocyte migration and chemokine activity for subcluster SOM9, Cytokine-cytokine receptor interaction for subcluster H2, and interleukin production, chemotaxis of immune cells, Chemokine signaling pathway and C-type lectin receptor signaling pathway for subcluster H3-K17-SOM1.Conclusions: Clustering analysis of splenocyte microRNAs in pig reflected the key regulatory properties of subcluster miRNA molecules, as well as the important features in the immune regulation induced by acute and chronic infections of T. gondii. These results contribute to new insight into the identification of physiologic immune responses and maintenance of tolerance in pig spleen tissues during T. gondii infection.

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Systems-level immunomonitoring from acute to recovery phase of severe COVID-19

10.1101/2020.06.03.20121582 ◽

2020 ◽

Cited By ~ 7

Author(s):

Lucie Rodriguez ◽

Pirkka Pekkarinen ◽

Tadepally Lakshmikanth ◽

Ziyang Tan ◽

Camila Rosat Consiglio ◽

...

Keyword(s):

Immune Response ◽

Immune Cell ◽

Inflammatory Responses ◽

Severe Disease ◽

Recovery Phase ◽

Sudden Onset ◽

The Many ◽

Humoral Responses ◽

Disease Stages ◽

Cell Cell

SUMMARYThe immune response to SARS-CoV2 is under intense investigation, but not fully understood att this moment. Severe disease is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5–7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome, rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Systems-level analyses are required to simultaneously capture all immune cell populations and the many protein mediators by which cells communicate. Since every patient analyzed will be captured at different stages of his or her infection, longitudinal monitoring of the immune response is critical. Here we report on a systems-level blood immunomonitoring study of 39 adult patients, hospitalized with severe COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFNγ – Eosinophil axis activated prior to lung hyperinflammation and changes in cell-cell coregulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.HIGHLIGHTSSystems-level immunomonitoring from acute to recovery in severe COVID-19An IFNγ - Eosinophil axis involved in lung hyperinflammationCell-cell coregulation differ during four disease stagesBasophils and hyperinflammation modulate humoral responsesA shared trajectory of immunological recovery in severe COVID-19

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Immune Responses of HIV-1 Tat Transgenic Mice to Mycobacterium Tuberculosis W-Beijing SA161

The Open AIDS Journal ◽

10.2174/1874613601105010086 ◽

2011 ◽

Vol 5 (1) ◽

pp. 86-95 ◽

Cited By ~ 1

Author(s):

Jennifer R Honda ◽

Shaobin Shang ◽

Crystal A Shanley ◽

Megan L Caraway ◽

Marcela Henao-Tamayo ◽

...

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Transgenic Mice ◽

Immune Responses ◽

Inflammatory Responses ◽

Intracellular Cytokine Staining ◽

Infectious Agent ◽

Microbial Pathogens ◽

Viral Gene ◽

Alveolar Cells

Background:Mycobacterium tuberculosisremains among the leading causes of death from an infectious agent in the world and exacerbates disease caused by the human immunodeficiency virus (HIV). HIV infected individuals are prone to lung infections by a variety of microbial pathogens, includingM. tuberculosis. While the destruction of the adaptive immune response by HIV is well understood, the actual pathogenesis of tuberculosis in co-infected individuals remains unclear. Tat is an HIV protein essential for efficient viral gene transcription, is secreted from infected cells, and is known to influence a variety of host inflammatory responses. We hypothesize Tat contributes to pathophysiological changes in the lung microenvironment, resulting in impaired host immune responses to infection byM. tuberculosis.Results:Herein, we show transgenic mice that express Tat by lung alveolar cells are more susceptible than non-transgenic control littermates to a low-dose aerosol infection ofM. tuberculosisW-Beijing SA161. Survival assays demonstrate accelerated mortality rates of the Tat transgenic mice compared to non-transgenics. Tat transgenic mice also showed poorly organized lung granulomata-like lesions. Analysis of the host immune response using quantitative RT-PCR, flow cytometry for surface markers, and intracellular cytokine staining showed increased expression of pro-inflammatory cytokines in the lungs, increased numbers of cells expressing ICAM1, increased numbers of CD4+CD25+Foxp3+ T regulatory cells, and IL-4 producing CD4+ T cells in the Tat transgenics compared to infected non-tg mice.Conclusions:Our data show quantitative differences in the inflammatory response to the SA161 clinical isolate ofM. tuberculosisW-Beijing between Tat transgenic and non-transgenic mice, suggesting Tat contributes to the pathogenesis of tuberculosis.

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Human immune response to SARS-CoV-2 infection

Jurnal Teknologi Laboratorium ◽

10.29238/teknolabjournal.v9i1.223 ◽

2020 ◽

Vol 9 (1) ◽

pp. 29-40

Author(s):

Lia Yosaneri Wina Nurtias ◽

Dora Dayu Rahma Turista ◽

Eka Puspitasari

Keyword(s):

Immune Response ◽

Immune Responses ◽

Severe Disease ◽

Adaptive Immune Response ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Reactive Protein ◽

Narrative Literature ◽

Human Immune Response ◽

Narrative Literature Review

COVID-19 is an acute respiratory infection caused by a new type of Coronavirus, SARS-CoV-2, which first appeared in Wuhan, China in December 2019. COVID-19 then became a pandemic in various countries in early 2020. In this article it contains review that discusses the immune response in humans due to SARS-CoV-2 infection, using the narrative literature review method, a total of 36 articles (6 from Elsevier, 24 from PMC, and 6 from Springer). It is known that the pathogenesis of COVID-19 and the manufacture of drugs and vaccines are still under investigation, but in infected patients, innate immune responses in the form of alveolar macrophages, dendritic cells, airway epithelial cells, congenital lymphocytes, and neutrophils work together in the fight against infection. Next comes the adaptive immune response in the form of antibodies (immunoglobulins) which help in fighting infections due to SARS-CoV-2. These immune responses include increasing levels of cytokines, coagulation parameters, C-reactive protein, neutrophils, and decreasing total lymphocytes. It is also known that COVID-19 patients with severe disease often experience higher total antibody, IgM responses, and IgG responses than COVID-19 patients without congenital disease. IgG antibodies are present in the serum, so the serum in COVID-19 patients who have recovered can be used for therapy in COVID-19 patients who have not healed, as long as the drug and vaccine are under investigation.

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