The network structure and eco-evolutionary dynamics of CRISPR-induced immune diversification

AbstractAs a heritable sequence-specific adaptive immune system, CRISPR-Cas is a powerful force shaping strain diversity in host-virus systems. While the diversity of CRISPR alleles has been explored, the associated structure and dynamics of host-virus interactions have not. We explore the role of CRISPR in mediating the interplay between host-virus interaction structure and eco-evolutionary dynamics in a computational model and compare results with three empirical datasets from natural systems. We show that the structure of the networks describing who infects whom and the degree to which strains are immune, are respectively modular (containing groups of hosts and viruses that interact strongly) and weighted-nested (specialist hosts are more susceptible to subsets of viruses that in turn also infect the more generalist hosts with many spacers matching many viruses). The dynamic interplay between these networks influences transitions between dynamical regimes of virus diversification and host control. The three empirical systems exhibit weighted-nested protection networks, a pattern our theory shows is indicative of hosts able to suppress virus diversification. Previously missing from studies of microbial host-pathogen systems, the protection network plays a key role in the coevolutionary dynamics.

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Role of Mitochondria in Viral Infections

Life ◽

10.3390/life11030232 ◽

2021 ◽

Vol 11 (3) ◽

pp. 232

Author(s):

Srikanth Elesela ◽

Nicholas W. Lukacs

Keyword(s):

Viral Infections ◽

Mitochondrial Dynamics ◽

The Body ◽

Viral Diseases ◽

Multiple Organs ◽

Innate Immune Signaling ◽

Mitochondrial Functions ◽

Host Virus Interactions ◽

Virus Interactions

Viral diseases account for an increasing proportion of deaths worldwide. Viruses maneuver host cell machinery in an attempt to subvert the intracellular environment favorable for their replication. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections. Viruses affect mitochondrial functions and impact mitochondrial metabolism, and innate immune signaling. Resurgence of host-virus interactions in recent literature emphasizes the key role of mitochondria and host metabolism on viral life processes. Mitochondrial dysfunction leads to damage of mitochondria that generate toxic compounds, importantly mitochondrial DNA, inducing systemic toxicity, leading to damage of multiple organs in the body. Mitochondrial dynamics and mitophagy are essential for the maintenance of mitochondrial quality control and homeostasis. Therefore, metabolic antagonists may be essential to gain a better understanding of viral diseases and develop effective antiviral therapeutics. This review briefly discusses how viruses exploit mitochondrial dynamics for virus proliferation and induce associated diseases.

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Adipocytes, Innate Immunity and Obesity: A Mini-Review

Frontiers in Immunology ◽

10.3389/fimmu.2021.650768 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alecia M. Blaszczak ◽

Anahita Jalilvand ◽

Willa A. Hsueh

Keyword(s):

Adipose Tissue ◽

Immune System ◽

Immune Cells ◽

Adaptive Immune System ◽

Innate Immune ◽

Lymphoid Cells ◽

Innate Immune Cells ◽

Adaptive Immune

The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.

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Evolution during primary HIV infection does not require adaptive immune selection

10.1101/2020.12.07.20245480 ◽

2020 ◽

Author(s):

David A Swan ◽

Morgane Rolland ◽

Joshua Herbeck ◽

Joshua T Schiffer ◽

Daniel B Reeves

Keyword(s):

Viral Load ◽

Immune System ◽

Hiv Infection ◽

Evolutionary Dynamics ◽

Immune Cell ◽

Adaptive Immune System ◽

Viral Fitness ◽

Immune Cell Population ◽

Adaptive Immune

AbstractModern HIV research depends crucially on both viral sequencing and population measurements. To directly link mechanistic biological processes and evolutionary dynamics during HIV infection, we developed multiple within-host phylodynamic (wi-phy) models of HIV primary infection for comparative validation against viral load and evolutionary dynamics data. The most parsimonious and accurate model required no positive selection, suggesting that the host adaptive immune system reduces viral load, but does not drive observed viral evolution. Rather, random genetic drift primarily dictates fitness changes. These results hold during early infection, and even during chronic infection when selection has been observed, viral fitness distributions are not largely different from in vitro distributions that emerge without adaptive immunity. These results highlight how phylogenetic inference must consider complex viral and immune-cell population dynamics to gain accurate mechanistic insights.One sentence summaryThrough the lens of a unified population and phylodynamic model, current data show the first wave of HIV mutations are not driven by selection by the adaptive immune system.

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A Role of Inflammation and Immunity in Essential Hypertension—Modeled and Analyzed Using Petri Nets

International Journal of Molecular Sciences ◽

10.3390/ijms21093348 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3348

Author(s):

Dorota Formanowicz ◽

Agnieszka Rybarczyk ◽

Marcin Radom ◽

Piotr Formanowicz

Keyword(s):

Essential Hypertension ◽

Adaptive Immune System ◽

Low Grade ◽

Kinin System ◽

Reactive Protein ◽

Adaptive Immune ◽

Key Enzyme ◽

Kallikrein Kinin System ◽

Low Grade Inflammation

Recent studies have shown that the innate and adaptive immune system, together with low-grade inflammation, may play an important role in essential hypertension. In this work, to verify the importance of selected factors for the development of essential hypertension, we created a Petri net-based model and analyzed it. The analysis was based mainly on t-invariants, knockouts of selected fragments of the net and its simulations. The blockade of the renin-angiotensin (RAA) system revealed that the most significant effect on the emergence of essential hypertension has RAA activation. This blockade affects: (1) the formation of angiotensin II, (2) inflammatory process (by influencing C-reactive protein (CRP)), (3) the initiation of blood coagulation, (4) bradykinin generation via the kallikrein-kinin system, (5) activation of lymphocytes in hypertension, (6) the participation of TNF alpha in the activation of the acute phase response, and (7) activation of NADPH oxidase—a key enzyme of oxidative stress. On the other hand, we found that the blockade of the activation of the RAA system may not eliminate hypertension that can occur due to disturbances associated with the osmotically independent binding of Na in the interstitium. Moreover, we revealed that inflammation alone is not enough to trigger primary hypertension, but it can coexist with it. We believe that our research may contribute to a better understanding of the pathology of hypertension. It can help identify potential subprocesses, which blocking will allow better control of essential hypertension.

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Role of immune cells in the ocular manifestations of pemphigoid diseases

Therapeutic Advances in Ophthalmology ◽

10.1177/2515841419868128 ◽

2019 ◽

Vol 11 ◽

pp. 251584141986812

Author(s):

Tanima Bose

Keyword(s):

Immune System ◽

Immune Cells ◽

Γδ T Cells ◽

Adaptive Immune System ◽

Mucous Membrane Pemphigoid ◽

Adaptive Immune ◽

Ocular Manifestations ◽

Different Types ◽

Ocular Distribution

Pemphigoid disease is classified according to the phenotypical location of the disease and the presence of different types of antibodies. The ocular distribution of pemphigoid mainly occurs in patients with bullous pemphigoid and mucous membrane pemphigoid. Several immune cells, including the cells of the innate immune system (neutrophils and γδ T cells) and the adaptive immune system (T and B cells), are involved in pemphigoid disease. The treatment of pemphigoid is still wide-ranging, and the most utilized treatment is the use of immunosuppressants and corticosteroids. In this scenario, it is absolutely important to screen the immune cells that are involved in this group of diseases and to determine if a targeted treatment approach is plausible. In conclusion, this review will identify some newer treatment possibilities for the whole spectrum of pemphigoid diseases.

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Role of the adaptive immune system in hypertension

Current Opinion in Pharmacology ◽

10.1016/j.coph.2010.01.006 ◽

2010 ◽

Vol 10 (2) ◽

pp. 203-207 ◽

Cited By ~ 108

Author(s):

David G Harrison ◽

Antony Vinh ◽

Heinrich Lob ◽

Meena S Madhur

Keyword(s):

Immune System ◽

Adaptive Immune System ◽

Adaptive Immune

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Role of T Lymphocytes in Type 2 Diabetes and Diabetes-Associated Inflammation

Journal of Diabetes Research ◽

10.1155/2017/6494795 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 52

Author(s):

Chang Xia ◽

Xiaoquan Rao ◽

Jixin Zhong

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

T Cells ◽

Immune System ◽

Critical Role ◽

Adaptive Immune System ◽

Metabolic Inflammation ◽

Adaptive Immune

Although a critical role of adaptive immune system has been confirmed in driving local and systemic inflammation in type 2 diabetes and promoting insulin resistance, the underlying mechanism is not completely understood. Inflammatory regulation has been focused on innate immunity especially macrophage for a long time, while increasing evidence suggests T cells are crucial for the development of metabolic inflammation and insulin resistance since 2009. There was growing evidence supporting the critical implication of T cells in the pathogenesis of type 2 diabetes. We will discuss the available effect of T cells subsets in adaptive immune system associated with the procession of T2DM, which may unveil several potential strategies that could provide successful therapies in the future.

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