Stress Response and Immunity: Links and Trade Offs

Nadia Danilova

• Publisher: Bentham Science Publishers
• Year: 2020
• Print ISBN:
  9789811437151
• eBook ISBN:
  9789811437175
• Topic: Scienze biologiche
• Subtopic: Biologia

When environmental conditions deviate from the optimal range, stress ensues. Stress response is a set of reactions that allow the organism to adjust and survive adverse conditions. Stress can be physical, such as extreme temperature, radiation, injury, or psychological, caused by perceived danger or deprivation. Every living cell has biochemical mechanisms to cope with physical stress. These mechanisms show a degree of similarity among several types of living organisms. Stress Response and Immunity: Links and Trade Offs explores the functional and evolutionary connections between stress response and immunity. The book introduces the reader to the concept of stress and subsequently examines the connection between stress response and immunity at various evolutionary stages of living organisms - from bacteria to humans. The book also features chapters dedicated to the role of tumor suppressor genes and the immune system of the brain. The information presented in this reference demonstrates the profound effects of physical and psychological stress on human health. Readers with basic knowledge of molecular biology will learn about the interesting facets of stress responses and the evolutionary trade offs observed in different life forms.

Autonomous Immunity

Nadia Danilova

Abstract

Autonomous immunity is a set of immune mechanisms present in practically every cell of a multicellular organism. They include immune mechanisms based on nuclear acids, such as RNA interference (RNAi). Small RNAs generated from pathogen dsRNAs guide nucleases to the pathogenic nucleic acids. In addition, RNAi restricts the expression of transposable elements by establishing transcription-repressing chromatin over DNA regions that encode such elements. Other autonomous mechanisms prevent the entry of viruses into cells, detect and destroy non-self nucleic acids, restrict pathogen growth and replication, prevent pathogen release, and induce regulated cell death if the infection cannot be suppressed. Infected cells release interferons and other cytokines that alert neighboring cells and preventively induce defensive mechanisms in them. Pathogens express pathogen-associated molecular patterns (PAMPs), which are recognized by pattern-recognition receptors (PRRs). These receptors also recognize damaged “self” molecules expressing damage-associated molecular patterns. Infection can also be sensed indirectly through changes in the functioning of some key cellular molecules. Stress and infection can lead to the formation of inflammasomes triggering production and secretion of pro-inflammatory cytokines.

Keywords: Argonaute, Drosha, Dicer, Damage-associated molecular pattern, Danger theory, Effector immunity, Inflammasome, NLR, Pathogen-associated molecular patterns, Pattern recognition receptor, piRNAs, RNA interference, siRNAs, TLR.

INTRODUCTION

Multicellular organisms have multiple mechanisms to protect themselves from infection. Animals have specialized innate and adaptive immune systems that include immune cells and humoral factors such as complement. Non-immune cells too have an impressive arsenal of immunodefense mechanisms. These mechanisms are called intrinsic or autonomous since many of them can function independently of cells and factors of specialized immune systems. Autonomous mechanisms are also present in immune cells, where they are integrated into cells’ function. Although being able to work independently, autonomous immune mechanisms typically communicate with the specialized immune systems through cytokines and other factors.

9.1. RNA Interference

Gene silencing based on small complementary RNA or DNA guides is an ancient regulatory principle. In bacteria and archaea, it is carried out by CRISPR-Cas and Argonaute (Ago)-based immunodefense systems presented in chapter five. DNA viruses, common in prokaryotes, are the main targets of these systems. With the expansion of RNA viruses in eukaryotes, Argonaute-based RNA interference (RNAi) systems have evolved [1, 2]. RNAi uses small RNA guides to cleave or downregulate RNA targets. RNA guides are produced from double-stranded RNAs by RNase-III-like endonucleases. RNAi systems evolve differently in various species: Caenorhabditis elegans has 27 Ago proteins whereas humans have only eight [3]. The modern RNAi branches into several specialized systems that include microRNAs (miRNAs) functioning as gene regulators, small interfering RNAs (siRNAs) functioning in antiviral defense, and PIWI-interacting RNAs (piRNAs) functioning in protection against transposable elements.

Most animal mRNAs are regulated by miRNAs, 21–23 nucleotide RNAs that have sequence complementarity to the 3′ UTRs of mRNAs [4]. miRNAs are typically transcribed as long primary transcripts (pri-miRNAs) from miRNA genes. pri-miRNAs are processed in the nucleus by the RNase-III-like endonuclease Drosha into approximately 70 nucleotide pre-miRNAs with stem-loop structures. Then, pre-miRNAs are transported from the nucleus to the cytoplasm and further processed by the second RNase Dicer into short duplexes. The guide strand of an miRNA duplex is loaded onto the RNA-induced silencing complex (RISC), where it guides Ago nucleases to the complementary mRNA transcripts to arrest their translation and/or accelerate their degradation by uncapping and deadenylation. miRNA function is regulated by post-translational modification of Ago proteins, alternative ways of miRNAs production and maturation, sequence editing, changes in miRNAs transport, modulation of their binding to targets, and through other means [5, 6].

miRNAs are involved in stress and immune response in multiple ways. Stress changes miRNA biogenesis. It can lead to miRNA modifications that influence its activity or specificity [7, 8]. miRNAs are involved in the regulation of p53 and NFκB networks [9^-11]. In response to DNA damage, p53 transcriptionally upregulates several miRNAs including miR-34 family [12]. miR-34a then regulates hundreds of genes that are involved in cell cycle arrest and apoptosis [13]. In addition, p53 interacts with Drosha complex and promotes post-transcriptional processing of several miRNAs with a growth-suppressing function such as miR-16-1 [14]. In contrast, p53 mutants interfere with Drosha complex assembly and miRNAs production. Correspondently, decreased miRNA levels are often observed in cancers with mutated p53.

miRNA biogenesis enzymes Drosha and Dicer are involved in DNA repair. They generate small RNAs at DNA double-strand break sites that are necessary for DNA repair [15].

In plants, miRNAs regulate the expression of immune disease resistance (R) genes. In the absence of infection, miRNAs suppress these genes [16]. In turn, overexpression of immune genes during infection suppresses miRNAs biosynthesis.

The small size of miRNAs means that they can migrate out of the cell into other cells and blood [17]. miRNAs from dying neurons are picked up by the astrocytes and interfere with their function [18]. Altered concentrations of some miRNAs in blood plasma may serve as a marker of Alzheimer’s disease [19].

RNAi, as an antiviral mechanism, has been discovered in plants and it provides the main protection against viruses in many species including, besides plants, nematodes, and arthropods [20, 21]. siRNAs are generated from pathogen dsRNAs, followed by their amplification by host RNA-directed RNA polymerase [22]. siRNAs differ from miRNAs by higher specificity. They usually cleave their targets before translation.

RNAi is used in a new plant protection technique where dsRNA corresponding to a pathogen’s protein is sprayed on the plant. This dsRNA is processed by the plant’s enzymes into siRNAs, which target the corresponding pathogen mRNA. dsRNA is delivered to the distal tissue through the plant vascular system and is processed there [23]. In vertebrates, RNAi participation in antiviral defense is often masked by concurrent mechanisms such as interferon system [24]. In stem cells, where the interferon system is inactive, RNAi plays an important role in antiviral defense [25]. Cellular miRNAs also can contribute to antiviral immunity by repressing host factors essential for viral replication [26, 27]. Many viruses encode factors suppressing R...

Table of contents

• Welcome
• Table of Content
• Title
• BENTHAM SCIENCE PUBLISHERS LTD.
• PREFACE
• Life is Stressful
• Pathogens
• How Bacteria Cope With Stress
• Extremophiles
• Immunodefenses of Prokaryotes
• Interaction of Stress and Immune Responses in Prokaryotes
• Response of Eukaryotes to Stress
• p53, Guardian of the Genome
• Autonomous Immunity
• Stress Response Meets Autonomous Immunity
• Specialized Immune Systems of Animals
• Brain, Stress, and Immunity Connections