scholarly journals A functional spleen contributes to afucosylated IgG in humans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iwona Wojcik ◽  
David E. Schmidt ◽  
Lisa A. de Neef ◽  
Minke A. E. Rab ◽  
Bob Meek ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Immune Cell ◽  
Lymphoid Organ ◽  
Immune Effector ◽  
Adaptive Immune ◽  
Wide Range ◽  
Humoral Responses ◽  
First Time

AbstractAs a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography–mass spectrometry (LC–MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.

scholarly journals MiR-146a in Immunity and Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Nicole Rusca ◽  
Silvia Monticelli
Keyword(s):  
Immune Responses ◽  
Recent Progress ◽  
Viral Infections ◽  
Cellular Functions ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Different Types ◽  
A Cell ◽  
And Function

MicroRNAs (miRNAs) are regulatory molecules able to influence all aspects of the biology of a cell. They have been associated with diseases such as cancer, viral infections, and autoimmune diseases, and in recent years, they also emerged as important regulators of immune responses. MiR-146a in particular is rapidly gaining importance as a modulator of differentiation and function of cells of the innate as well as adaptive immunity. Given its importance in regulating key cellular functions, it is not surprising that miR-146a expression was also found dysregulated in different types of tumors. In this paper, we summarize recent progress in understanding the role of miR-146a in innate and adaptive immune responses, as well as in disease.

scholarly journals Immune responses in COVID-19 respiratory tract and blood reveal mechanisms of disease severity

2021 ◽  
Author(s):  
Wuji Zhang ◽  
Brendon Chua ◽  
Kevin John Selva ◽  
Lukasz Kedzierski ◽  
Thomas Ashhurst ◽  
...  
Keyword(s):  
Immune Responses ◽  
Respiratory Tract ◽  
Immune Cell ◽  
Endotracheal Aspirate ◽  
Neutralization Activity ◽  
Adaptive Immune ◽  
Immune Cell Subsets ◽  
Iga Antibodies ◽  
Humoral Responses ◽  
Respiratory Specimens

Although the respiratory tract is the primary site of SARS-CoV-2 infection and the ensuing immunopathology, respiratory immune responses are understudied and urgently needed to understand mechanisms underlying COVID-19 disease pathogenesis. We collected paired longitudinal blood and respiratory tract samples (endotracheal aspirate, sputum or pleural fluid) from hospitalized COVID-19 patients and non-COVID-19 controls. Cellular, humoral and cytokine responses were analysed and correlated with clinical data. SARS-CoV-2-specific IgM, IgG and IgA antibodies were detected using ELISA and multiplex assay in both the respiratory tract and blood of COVID-19 patients, although a higher receptor binding domain (RBD)-specific IgM and IgG seroconversion level was found in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples was detected only when high levels of RBD-specific antibodies were present. Strikingly, cytokine/chemokine levels and profiles greatly differed between respiratory samples and plasma, indicating that inflammation needs to be assessed in respiratory specimens for the accurate assessment of SARS-CoV-2 immunopathology. Diverse immune cell subsets were detected in respiratory samples, albeit dominated by neutrophils. Importantly, we also showed that dexamethasone and/or remdesivir treatment did not affect humoral responses in blood of COVID-19 patients. Overall, our study unveils stark differences in innate and adaptive immune responses between respiratory samples and blood and provides important insights into effect of drug therapy on immune responses in COVID-19 patients.

scholarly journals Toll-Like Receptors: Are They Taking a Toll on the Heart in Viral Myocarditis?

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1003
Author(s):  
Kasper Favere ◽  
Matthias Bosman ◽  
Karin Klingel ◽  
Stephane Heymans ◽  
Sophie Van Linthout ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Viral Myocarditis ◽  
Disease Process ◽  
Future Research ◽  
Toll Like Receptors ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Evolutionarily Conserved

Myocarditis is an inflammatory disease of the heart with viral infections being the most common aetiology. Its complex biology remains poorly understood and its clinical management is one of the most challenging in the field of cardiology. Toll-like receptors (TLRs), a family of evolutionarily conserved pattern recognition receptors, are increasingly known to be implicated in the pathophysiology of viral myocarditis. Their central role in innate and adaptive immune responses, and in the inflammatory reaction that ensues, indeed makes them prime candidates to profoundly affect every stage of the disease process. This review describes the pathogenesis and pathophysiology of viral myocarditis and scrutinises the role of TLRs in every phase. We conclude with directions for future research in this field.

scholarly journals Regulation of Antiviral Immune Response by N6-Methyladenosine of mRNA

2021 ◽  
Vol 12 ◽  
Author(s):  
Baoxin Zhao ◽  
Weijie Wang ◽  
Yan Zhao ◽  
Hongxiu Qiao ◽  
Zhiyun Gao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infection ◽  
Viral Infections ◽  
Immune Cell ◽  
Vital Role ◽  
Immune Defense ◽  
Interferon Response ◽  
Adaptive Immune Responses ◽  
Antiviral Immune Response ◽  
Adaptive Immune

Host innate and adaptive immune responses play a vital role in clearing infected viruses. Meanwhile, viruses also evolve a series of mechanisms to weaken the host immune responses and evade immune defense. Recently, N6-methyladenosine (m6A), the most prevalent mRNA modification, has been revealed to regulate multiple steps of RNA metabolism, such as mRNA splicing, localization, stabilization, and translation, thus participating in many biological phenomena, including viral infection. In the process of virus–host interaction, the m6A modification that presents on the virus RNA impedes capture by the pattern recognition receptors, and the m6A modification appearing on the host immune-related molecules regulate interferon response, immune cell differentiation, inflammatory cytokine production, and other immune responses induced by viral infection. This review summarizes the research advances about the regulatory role of m6A modification in the innate and adaptive immune responses during viral infections.

scholarly journals Immune responses in COVID-19 respiratory tract and blood reveal mechanisms of disease severity

2021 ◽  
Author(s):  
Wuji Zhang ◽  
Brendon Chua ◽  
Kevin Selva ◽  
Lukasz Kedzierski ◽  
Thomas Ashhurst ◽  
...  
Keyword(s):  
Immune Responses ◽  
Respiratory Tract ◽  
Immune Cell ◽  
Endotracheal Aspirate ◽  
Neutralization Activity ◽  
Adaptive Immune ◽  
Immune Cell Subsets ◽  
Iga Antibodies ◽  
Humoral Responses ◽  
Respiratory Specimens

Abstract Although the respiratory tract is the primary site of SARS-CoV-2 infection and the ensuing immunopathology, respiratory immune responses are understudied and urgently needed to understand mechanisms underlying COVID-19 disease pathogenesis. We collected paired longitudinal blood and respiratory tract samples (endotracheal aspirate, sputum or pleural fluid) from hospitalized COVID-19 patients and non-COVID-19 controls. Cellular, humoral and cytokine responses were analysed and correlated with clinical data. SARS-CoV-2-specific IgM, IgG and IgA antibodies were detected using ELISA and multiplex assay in both the respiratory tract and blood of COVID-19 patients, although a higher receptor binding domain (RBD)-specific IgM and IgG seroconversion level was found in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples was detected only when high levels of RBD-specific antibodies were present. Strikingly, cytokine/chemokine levels and profiles greatly differed between respiratory samples and plasma, indicating that inflammation needs to be assessed in respiratory specimens for the accurate assessment of SARS-CoV-2 immunopathology. Diverse immune cell subsets were detected in respiratory samples, albeit dominated by neutrophils. Importantly, we also showed that dexamethasone and/or remdesivir treatment did not affect humoral responses in blood of COVID-19 patients. Overall, our study unveils stark differences in innate and adaptive immune responses between respiratory samples and blood and provides important insights into effect of drug therapy on immune responses in COVID-19 patients.

scholarly journals Classical dendritic cells as a unique immune cell lineage

2012 ◽  
Vol 209 (6) ◽  
pp. 1053-1056 ◽  
Author(s):  
Boris Reizis
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Immune Cell ◽  
Critical Role ◽  
Cell Lineage ◽  
Specific Pattern ◽  
Adaptive Immune ◽  
Definition Of

Despite the critical role of classical dendritic cells (cDCs) in the initiation of adaptive immune responses, the genetic and phenotypic definition of cDCs remains moot. Two new studies designate Zbtb46 as a novel transcription factor that is specifically expressed in all cDCs in both humans and mice. Although Zbtb46 appears dispensable for cDC development, its specific pattern of expression supports the notion that cDCs constitute a unique immune cell lineage. Furthermore, these two studies provide novel tools that will aid in the study of cDC progenitors, visualization of cDCs in vivo, and depletion of cDCs for functional analysis.

scholarly journals CD8+ lymphocytes modulate Zika virus dynamics and tissue dissemination and orchestrate antiviral immunity

2018 ◽  
Author(s):  
Blake Schouest ◽  
Marissa Fahlberg ◽  
Elizabeth A. Scheef ◽  
Matthew J. Ward ◽  
Kyra Headrick ◽  
...  
Keyword(s):  
Immune Responses ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Viral Infections ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Acute Infection ◽  
Transcriptional Responses ◽  
Adaptive Immune ◽  
Cd8 Depletion

AbstractCD8+ lymphocytes are critically important in the control of viral infections, but their roles in acute Zika virus (ZIKV) infection remain incompletely explored in a model sufficiently similar to humans immunologically. Here, we use CD8+ lymphocyte depletion to dissect acute immune responses in adult male rhesus and cynomolgus macaques infected with ZIKV. CD8 depletion delayed serum viremia and dysregulated patterns of innate immune cell homing and monocyte-driven transcriptional responses in the blood. CD8-depleted macaques also showed evidence of compensatory adaptive immune responses, with elevated Th1 activity and persistence of neutralizing antibodies beyond the clearance of serum viremia. The absence of CD8+ lymphocytes increased viral burdens in lymphatic tissues, semen, and cerebrospinal fluid, and neural lesions were also evident in both CD8-depleted rhesus macaques. Together, these data support a role for CD8+ lymphocytes in the control of ZIKV dissemination and in maintaining immune regulation during acute infection of nonhuman primates.

scholarly journals Role of the Innate Immunity Signaling Pathway in the Pathogenesis of Sjögren’s Syndrome

2021 ◽  
Vol 22 (6) ◽  
pp. 3090
Author(s):  
Toshimasa Shimizu ◽  
Hideki Nakamura ◽  
Atsushi Kawakami
Keyword(s):  
Immune Responses ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Innate Immune ◽  
Type I ◽  
Type I Ifn ◽  
Adaptive Immune ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands and extra-glandular lesions. Adaptive immune response including T- and B-cell activation contributes to the development of SS. However, its pathogenesis has not yet been elucidated. In addition, several patients with SS present with the type I interferon (IFN) signature, which is the upregulation of the IFN-stimulated genes induced by type I IFN. Thus, innate immune responses including type I IFN activity are associated with SS pathogenesis. Recent studies have revealed the presence of activation pattern recognition receptors (PRRs) including Toll-like receptors, RNA sensor retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, and inflammasomes in infiltrating and epithelial cells of the salivary glands among patients with SS. In addition, the activation of PRRs via the downstream pathway such as the type I IFN signature and nuclear factor kappa B can directly cause organ inflammation, and it is correlated with the activation of adaptive immune responses. Therefore, this study assessed the role of the innate immune signal pathway in the development of inflammation and immune abnormalities in SS.

scholarly journals Insights into Antibody-Mediated Alphavirus Immunity and Vaccine Development Landscape

2021 ◽  
Vol 9 (5) ◽  
pp. 899
Author(s):  
Anthony Torres-Ruesta ◽  
Rhonda Sin-Ling Chee ◽  
Lisa F.P. Ng
Keyword(s):  
Diagnostic Tests ◽  
Inflammatory Arthritis ◽  
Chikungunya Virus ◽  
Vaccine Development ◽  
Antibody Responses ◽  
Chikv Infection ◽  
Wide Range ◽  
Susceptible Populations ◽  
Humoral Responses

Alphaviruses are mosquito-borne pathogens distributed worldwide in tropical and temperate areas causing a wide range of symptoms ranging from inflammatory arthritis-like manifestations to the induction of encephalitis in humans. Historically, large outbreaks in susceptible populations have been recorded followed by the development of protective long-lasting antibody responses suggesting a potential advantageous role for a vaccine. Although the current understanding of alphavirus antibody-mediated immunity has been mainly gathered in natural and experimental settings of chikungunya virus (CHIKV) infection, little is known about the humoral responses triggered by other emerging alphaviruses. This knowledge is needed to improve serology-based diagnostic tests and the development of highly effective cross-protective vaccines. Here, we review the role of antibody-mediated immunity upon arthritogenic and neurotropic alphavirus infections, and the current research efforts for the development of vaccines as a tool to control future alphavirus outbreaks.

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