scholarly journals Fate mapping of single NK cells identifies a type 1 innate lymphoid-like lineage that bridges innate and adaptive recognition of viral infection

Immunity ◽  
2021 ◽  
Author(s):  
Sophie Flommersfeld ◽  
Jan P. Böttcher ◽  
Jonatan Ersching ◽  
Michael Flossdorf ◽  
Philippa Meiser ◽  
...  
Keyword(s):  
Viral Infection ◽  
Nk Cells ◽  
Fate Mapping ◽  
Adaptive Recognition

Hobit confers tissue-dependent programs to type 1 innate lymphoid cells

2021 ◽  
Vol 118 (50) ◽  
pp. e2117965118
Author(s):  
Kentaro Yomogida ◽  
Tarin M. Bigley ◽  
Tihana Trsan ◽  
Susan Gilfillan ◽  
Marina Cella ◽  
...  
Keyword(s):  
Viral Infection ◽  
Nk Cells ◽  
Salivary Glands ◽  
Intestinal Mucosa ◽  
Nk Cell ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Unique Cell ◽  
The Impact

Identification of type 1 innate lymphoid cells (ILC1s) has been problematic. The transcription factor Hobit encoded by Zfp683 has been proposed as a major driver of ILC1 programs. Using Zfp683 reporter mice, we showed that correlation of Hobit expression with ILC1s is tissue- and context-dependent. In liver and intestinal mucosa, Zfp683 expression correlated well with ILC1s; in salivary glands, Zfp683 was coexpressed with the natural killer (NK) master transcription factors Eomes and TCF1 in a unique cell population, which we call ILC1-like NK cells; during viral infection, Zfp683 was induced in conventional NK cells of spleen and liver. The impact of Zfp683 deletion on ILC1s and NK cells was also multifaceted, including a marked decrease in granzyme- and interferon-gamma (IFNγ)–producing ILC1s in the liver, slightly fewer ILC1s and more Eomes+ TCF1+ ILC1-like NK cells in salivary glands, and only reduced production of granzyme B by ILC1 in the intestinal mucosa. NK cell–mediated control of viral infection was unaffected. We conclude that Hobit has two major impacts on ILC1s: It sustains liver ILC1 numbers, while promoting ILC1 functional maturation in other tissues by controlling TCF1, Eomes, and granzyme expression.

575 Regression by hetIL-15 monotherapy in different mouse breast cancer models correlates with intratumoral infiltration of a novel population of dendritic cells

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A609-A609
Author(s):  
Sevasti Karaliota ◽  
Dimitris Stellas ◽  
Vasiliki Stravokefalou ◽  
Bethany Nagy ◽  
Cristina Bergamaschi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dendritic Cells ◽  
Nk Cells ◽  
Flow Analysis ◽  
Laboratory Animals ◽  
Tumor Infiltration ◽  
The Novel ◽  
Phenotypic Profile ◽  
Conventional Type

BackgroundIL-15 is a cytokine which stimulates the proliferation and cytotoxic function of CD8+ T and NK cells. We have produced and applied the native heterodimeric IL-15 (hetIL-15) on several preclinical models, which have supported the anti-tumor activity of hetIL-15. Based on these results, hetIL-15 has advanced to clinical trials. The objectives of this study were to explore how hetIL-15 shapes the tumor microenviroment and to characterize the interactions between tumor-infiltrating lymphoid and myeloid cells.MethodsWe studied the efficacy of locoregional administration of heterodimeric IL-15 (hetIL-15) in two different orthotopic triple-negative breast cancer (TNBC) mouse models, syngeneic for C57BL/6 and Balb/c, respectively. The effects of hetIL-15 on immune cells were analyzed by flow cytometry, immunohistochemistry (IHC) and gene expression profiling. The profile of the novel infiltrated dendritic cell populations was further explored by bulk and single cell RNAseq.Results hetIL-15 resulted in tumor eradication in 40% of treated mice and reduction of metastasis. Subsequent rechallenges with the same cell line failed to generate tumor regrowth, suggesting the development of immunological memory in hetIL-15 treated mice. hetIL-15 promoted tumor accumulation of proliferating and cytotoxic CD8+ T and NK cells. Additionally, peritumoral hetIL-15 administration resulted in an increased tumor infiltration of both conventional type 1 dendritic cells (cDC1s) and of a novel DC population found only in the hetIL-15 treated animals. Phenotypic profile analysis confirmed the expression of several cDC1 specific markers, including CD103 and IRF8 on this DC population.Transcriptomics and flow analysis of intratumoral dendritic cells indicate that the new hetIL-15 induced cells reside preferentially in the tumors and are distinct from cDC1 and cDC2 populations. Both cDC1s and the novel DC population were inversely correlated with the tumor size.ConclusionsLocoregional administration of hetIL-15 results in complete eradication of EO771 and significant reduction of 4T1 primary breast cancer tumors, prolonged survival and long-lasting specific anti-tumor immunity. hetIL-15 increases the tumor infiltration of activated T and NK cells and intensifies the tumor infiltration of conventional type 1 dendritic cells (cDC1) and a new population of dendritic cells. We propose that the anti-cancer activity of hetIL-15 in primary EO771 tumors is orchestrated by the interplay of NK, CD8+T cells, cDC1 and a novel subset of DCs with a distinct phenotypic profile. These findings suggest a role for hetIL-15 in the treatment of breast cancer.Ethics ApprovalThe study was approved by the National Cancer Institute-Frederick Animal Care and Use Committee, approval number 19–324 and was conducted in accordance with the ACUC guidelines and the NIH Guide for the Care and Use of Laboratory Animals.

scholarly journals A double-edged sword of immuno-microenvironment in cardiac homeostasis and injury repair

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kang Sun ◽  
Yi-yuan Li ◽  
Jin Jin
Keyword(s):  
Nk Cells ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Early Stage ◽  
Cardiac Injury ◽  
Inflammatory Cells ◽  
Treg Cells ◽  
Scar Formation

AbstractThe response of immune cells in cardiac injury is divided into three continuous phases: inflammation, proliferation and maturation. The kinetics of the inflammatory and proliferation phases directly influence the tissue repair. In cardiac homeostasis, cardiac tissue resident macrophages (cTMs) phagocytose bacteria and apoptotic cells. Meanwhile, NK cells prevent the maturation and transport of inflammatory cells. After cardiac injury, cTMs phagocytose the dead cardiomyocytes (CMs), regulate the proliferation and angiogenesis of cardiac progenitor cells. NK cells prevent the cardiac fibrosis, and promote vascularization and angiogenesis. Type 1 macrophages trigger the cardioprotective responses and promote tissue fibrosis in the early stage. Reversely, type 2 macrophages promote cardiac remodeling and angiogenesis in the late stage. Circulating macrophages and neutrophils firstly lead to chronic inflammation by secreting proinflammatory cytokines, and then release anti-inflammatory cytokines and growth factors, which regulate cardiac remodeling. In this process, dendritic cells (DCs) mediate the regulation of monocyte and macrophage recruitment. Recruited eosinophils and Mast cells (MCs) release some mediators which contribute to coronary vasoconstriction, leukocyte recruitment, formation of new blood vessels, scar formation. In adaptive immunity, effector T cells, especially Th17 cells, lead to the pathogenesis of cardiac fibrosis, including the distal fibrosis and scar formation. CMs protectors, Treg cells, inhibit reduce the inflammatory response, then directly trigger the regeneration of local progenitor cell via IL-10. B cells reduce myocardial injury by preserving cardiac function during the resolution of inflammation.

Non-susceptibility genes to Bombyx densovirus type 1, Nid-1 and nsd-1, affect distinct steps of the viral infection pathway

2010 ◽  
Vol 103 (1) ◽  
pp. 79-81 ◽  
Author(s):  
Kurako Kidokoro ◽  
Katsuhiko Ito ◽  
Dorington O. Ogoyi ◽  
Hiroaki Abe ◽  
Kazuei Mita ◽  
...  
Keyword(s):  
Viral Infection ◽  
Susceptibility Genes ◽  
Infection Pathway

scholarly journals Cure of Chronic Viral Infection and Virus-Induced Type 1 Diabetes by Neutralizing Antibodies

2006 ◽  
Vol 13 (1) ◽  
pp. 67-77 ◽  
Author(s):  
Mette Ejrnaes ◽  
Matthias G. von Herrath ◽  
Urs Christen
Keyword(s):  
Type 1 Diabetes ◽  
Viral Infection ◽  
Inflammatory Mediators ◽  
Neutralizing Antibodies ◽  
Chronic Viral Infection ◽  
Negative Consequences ◽  
Ligand Interactions ◽  
The Right

The use of neutralizing antibodies is one of the most successful methods to interfere with receptor–ligand interactions in vivo. In particular blockade of soluble inflammatory mediators or their corresponding cellular receptors was proven an effective way to regulate inflammation and/or prevent its negative consequences. However, one problem that comes along with an effective neutralization of inflammatory mediators is the general systemic immunomodulatory effect. It is, therefore, important to design a treatment regimen in a way to strike at the right place and at the right time in order to achieve maximal effects with minimal duration of immunosuppression or hyperactivation. In this review, we reflect on two examples of how short time administration of such neutralizing antibodies can block two distinct inflammatory consequences of viral infection. First, we review recent findings that blockade of IL-10/IL-10R interaction can resolve chronic viral infection and second, we reflect on how neutralization of the chemokine CXCL10 can abrogate virus-induced type 1 diabetes.

scholarly journals Probiotics and Paraprobiotics in Viral Infection: Clinical Application and Effects on the Innate and Acquired Immune Systems

2018 ◽  
Vol 24 (6) ◽  
pp. 710-717 ◽  
Author(s):  
Osamu Kanauchi ◽  
Akira Andoh ◽  
Sazaly AbuBakar ◽  
Naoki Yamamoto
Keyword(s):  
Infectious Diseases ◽  
Viral Infection ◽  
Human Ecology ◽  
Commensal Bacteria ◽  
Mutation Rates ◽  
Viral Diseases ◽  
Interferon Production ◽  
Unique Mechanism ◽  
Stimulation Of

Recently, the risk of viral infection has dramatically increased owing to changes in human ecology such as global warming and an increased geographical movement of people and goods. However, the efficacy of vaccines and remedies for infectious diseases is limited by the high mutation rates of viruses, especially, RNA viruses. Here, we comprehensively review the effectiveness of several probiotics and paraprobiotics (sterilized probiotics) for the prevention or treatment of virally-induced infectious diseases. We discuss the unique roles of these agents in modulating the cross-talk between commensal bacteria and the mucosal immune system. In addition, we provide an overview of the unique mechanism by which viruses are eliminated through the stimulation of type 1 interferon production by probiotics and paraprobiotics via the activation of dendritic cells. Although further detailed research is necessary in the future, probiotics and/or paraprobiotics are expected to be among the rational adjunctive options for the treatment of various viral diseases.

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