How plants recognize pathogens and defend themselves

Plants have an innate immunity system to defend themselves against pathogens. With the primary immune system, plants recognize microbe-associated molecular patterns (MAMPs) of potential pathogens through pattern recognition receptors (PRRs) that mediate a basal defense response. Plant pathogens suppress this basal defense response by means of effectors that enable them to cause disease. With the secondary immune system, plants have gained the ability to recognize effector-induced perturbations of host targets through resistance proteins (RPs) that mediate a strong local defense response that stops pathogen growth. Both primary and secondary immune responses in plants depend on germ line-encoded PRRs and RPs. During induction of local immune responses, systemic immune responses also become activated, which predispose plants to become more resistant to subsequent pathogen attacks. This review gives an update on recent findings that have enhanced our understanding of plant innate immunity and the arms race between plants and their pathogens. Received 24 June 2007; received after revision 18 July 2007; accepted 15 August 2007     

Regulatory mechanisms of mitogen-activated kinase signaling

MAP kinases (MAPKs) are evolutionarily conserved regulators that mediate signal transduction and play essential roles in various physiological processes. There are three main families of MAPKs in mammals, whose functions are regulated by activators, inactivators, substrates and scaffolds, which together form delicate signaling cascades in response to different extracellular or intracellular stimulation. MAPK signaling is tightly regulated so that optimal biological activities are achieved and health is maintained. However, how the specificity of the signaling flow along each cascade is achieved is still relatively unclear. In this review, we summarize recent advances in understanding the regulation of MAPK cascades and the roles of MAP kinases and their regulators in development and in immune responses. Received 11 January 2007; received after revision 31 May 2007; accepted 5 July 2007     

Intestinal epithelial barrier and mucosal immunity

The mucosal immune system maintains a delicate balance between providing robust defense against infectious pathogens and, at the same time, regulating responses toward innocuous environmental and food antigens and commensal microbes. The Peyer's patch (PP) has been studied in detail as a major inductive site for mucosal immunity within the small intestine. While the mechanisms responsible for the induction of mucosal immunity versus tolerance are not yet fully understood, recent studies have highlighted mucosal dendritic cells (DCs) as regulators of the immune responses to orally administered antigens. Here we discuss recent studies that describe the role of PP DCs in immune induction and speculate on the mechanism by which the resident DCs regulate T cell and immunoglobulin A (IgA) responses in the gastrointestinal mucosa.     

Signal perception in plant pathogen defense

Highly sensitive and specific recognition systems for microbial pathogens are essential for disease resistance in plants. Structurally diverse elicitors from various pathogens have been identified and shown to trigger plant defense mechanisms. Elicitor recognition by the plant is assumed to be mediated by receptors. Plant receptors for fungus-derived elicitors appear to reside preferentially in the plasma membrane, whereas viral and bacterial elicitors may enter the plant cell and are perceived intracellularly. Receptor activation initiates an intracellular signal transduction cascade leading to stimulation of a characteristic set of plant defense responses. Isolation of plant elicitor receptors and their encoding genes is expected to provide significant information on the molecular basis of signal perception and intracellular signal generation in plant-pathogen interactions.     

The peptidoglycan recognition proteins LCa and LCx

Infection of bacteria triggers innate immune defense reactions in Drosophila. So far, the only bacterial component known to be recognized by the insect innate immune system is peptidoglycan, one of the most abundant constituents of the bacterial cell wall. Insects use peptidoglycan recognition proteins to detect peptidoglycan and to activate innate immune responses. Such specialized peptidoglycan receptors appear to have evolved from phage enzymes that hydrolyze bacterial cell walls. They are able to bind specific peptidoglycan molecules with distinct chemical moieties and activate innate immune pathways by interacting with other signaling proteins. Recent X-ray crystallographic studies of the peptidoglycan recognition proteins LCa, and LCx bound to peptidoglycan have provided structural insights into recognition of peptidoglycan and activation of innate immunity in insects. Received 28 December 2006; received after revision 2 February 2007; accepted 21 February 2007     

Platelets in defense against bacterial pathogens

Platelets interact with bacterial pathogens through a wide array of cellular and molecular mechanisms. The consequences of this interaction may significantly influence the balance between infection and immunity. On the one hand, recent data indicate that certain bacteria may be capable of exploiting these interactions to gain a virulence advantage. Indeed, certain bacterial pathogens appear to have evolved specific ways in which to subvert activated platelets. Hence, it is conceivable that some bacterial pathogens exploit platelet responses. On the other hand, platelets are now known to possess unambiguous structures and functions of host defense effector cells. Recent discoveries emphasize critical features enabling such functions, including expression of toll-like receptors that detect hallmark signals of bacterial infection, an array of microbicidal peptides, as well as other host defense molecules and functions. These concepts are consistent with increased risk and severity of bacterial infection as correlates of clinical abnormalities in platelet quantity and quality. In these respects, the molecular and cellular roles of platelets in host defense against bacterial pathogens are explored with attention on advances in platelet immunobiology.     

Intestinal epithelial barrier and mucosal immunity

The innate immune system plays a crucial role in maintaining the integrity of the intestine and protecting the host against a vast number of potential microbial pathogens from resident and transient gut microflora. Mucosal epithelial cells and Paneth cells produce a variety of antimicrobial peptides (defensins, cathelicidins, crytdinrelated sequence peptides, bactericidal/permeabilityincreasing protein, chemokine CCL20) and bacteriolytic enzymes (lysozyme, group IIA phospholipase A2) that protect mucosal surfaces and crypts containing intestinal stem cells against invading microbes. Many of the intestinal antimicrobial molecules have additional roles of attracting leukocytes, alarming the adaptive immune system or neutralizing proinflammatory bacterial molecules. Dysfunction of components of the innate immune system has recently been implicated in chronic inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, illustrating the pivotal role of innate immunity in maintaining the delicate balance between immune tolerance and immune response in the gut.     

Cationic host defence peptides: Innate immune regulatory peptides as a novel approach for treating infections

An increase in antibiotic resistance and the emergence of new pathogens has led to an urgent need for alternative approaches to infection management. Immunomodulatory molecules that do not target the pathogen directly, but rather selectively enhance and/or alter host defence mechanisms, are attractive candidates for therapeutic development. Natural cationic host defence peptides represent lead molecules that boost innate immune responses and selectively modulate pathogen-induced inflammatory responses. This review discusses recent evidence exploring the mechanisms of cationic host defence peptides as innate immune regulators, their role in the interface of innate and adaptive immunity, and their potential application as beneficial therapeutics in overcoming infectious diseases. Received 3 November 2006; received after revision 14 December 2006; accepted 22 January 2007     

Mucosal effector memory T cells: the other side of the coin

Immunological memory allows for rapid and effective protective immunity to previously encountered pathogens. New insights in understanding specific memory differentiation and function have now indicated that in addition to providing enhanced immunity, an important purpose of immunological memory is to provide immediate protection at all sites of the body, including non-lymphoid tissues. Effector memory CD8 T cells have the capacity to reside long-term at epithelial surfaces, where they allow for rapid containment of the invading pathogens at the local entry site and prevent systemic spreading and excessive immune responses. The accumulation of tissue-specific memory T cell subsets, together with cross-reactivity of these antigen-experienced T cells even to unrelated pathogens, provides flexibility and expansion of their specificity repertoire that over time greatly surpasses that of the declining na?ve T cell populations. This review will discuss new insights into T cell memory. We will focus in particular on the generation and function of effector memory CD8 T cells at the intestinal mucosa, which represents one of the largest entry sites for pathogens.     

<Emphasis Type="Italic">The Art of War:</Emphasis> Innate and adaptive immune responses

Research over the last several years has greatly advanced our understanding of the mechanisms by which the immune system functions. There exist two main branches of immunity, termed innate and adaptive immunity. Innate immunity uses the genetic memory of germline-encoded receptors to recognize the molecular patterns of common pathogens. Adaptive immunity, akin to somatic memory, is a complex system by which the body learns to recognize a pathogens unique antigens and builds an antigen specific response to destroy it. The effective development of the overall immune response depends on careful interplay and regulation between innate and adaptive immunity. Here we review our current understanding of how these integrated systems distinguish targets against which a response is appropriate and neutralize potentially pathogenic challenges.Received 8 May 2003; accepted 2 June 2003     

Antigen-specific T cells in autoimmune diseases with a focus on multiple sclerosis and experimental allergic encephalomyelitis

Although the pathogenesis of autoimmune diseases remains poorly understood, the current view is that autoaggresive antigen-specific T cells play a central role in the cascade of events leading to most autoimmune diseases. A major event in the development of autoimmune diseases is the activation of antigen-specific T cells-how, when and where does this activation take place? This review addresses questions concerning the occurrence of unique autoantigens triggering autoimmune diseases, the factors influencing the balance between self-tolerance and autoaggresive immunity, and the mechanisms by which dendritic cells mediate immunity and tolerance to antigen-specific T cells. Knowledge of how antigen-specific T cells are activated is now being used to develop therapeutic approaches to control autoimmune diseases. We discuss tolerance to antigen-specific T cells and tolerance induction as treatment of T-cell-mediated autoimmune diseases. Therapeutic modalities have been established which selectively target the pathogenic T cells. leaving the remainder of the immune system intact.     

MAP kinases in plant signal transduction

Mitogen-activated protein kinase (MAPK) pathways are modules involved in the transduction of extracellular signals to intracellular targets in all eukaryotes. Distinct MAPK pathways are regulated by different extracellular stimuli and are implicated in a wide variety of biological processes. In plants there is evidence for MAPKs playing a role in the signaling of abiotic stresses, pathogens and plant hormones. The large number and divergence of plant MAPKs indicates that this ancient mechanism of bioinformatics is extensively used in plants and may provide a new molecular handle on old questions.     

An ancient cytokine,astakine, mediates circadian regulation of invertebrate hematopoiesis

Invertebrate circulating hemocytes are key players in the innate immune defense and their continuous renewal from hematopoietic tissues is tightly regulated in crustaceans by astakine, a new family of cytokines sharing a prokineticin (PROK) domain. In vertebrates, brain PROKs function as transmitters of circadian rhythms and we present evidence that hemocyte release from hematopoietic tissues in crayfish is under circadian regulation, a direct result of rhythmic expression of astakine. We demonstrate that the observed variation in astakine expression has an impact on innate immunity assessed as susceptibility to a pathogenic Pseudomonas species. These findings enlighten the importance of comparing immune responses at fixed times not to neglect circadian regulation of innate immunity. Moreover, our results entail an evolutionary conserved function for prokineticins as mediators of circadian rhythm, and for the first time show a role for this domain in circadian regulation of hematopoiesis that may have implications also in vertebrates.     

Leukotrienes: Mediators that have been typecast as villains

As befalls many mediators that act upon the human stage, leukotrienes have become identified with their most powerful roles as villains of the immune system. They are well known for their leading roles in allergic diseases, including asthma. They also have gained recognition for their dramatic role as promoters of inflammation. As new roles for these lipid messengers are sought, it is becoming apparent that the leukotrienes have been typecast as bad guys of the immune system. As examples, their more recent roles have been in atherosclerosis, pulmonary fibrosis and cancer. However, upon further evaluation, we can begin to see their versatility. Thus, leukotrienes stimulate innate immunity against pathogens. In addition, they promote the expression of mediators, receptors and other molecules that are important for immune defense. In these lesser known roles, they lead the fight against bacterial, fungal and viral infection. This review is intended to shed light on the leukotrienes, where they come from and what we really know about them.     

The p38/MAPK pathway regulates microtubule polymerization through phosphorylation of MAP4 and Op18 in hypoxic cells

In both cardiomyocytes and HeLa cells, hypoxia (1% O₂) quickly leads to microtubule disruption, but little is known about how microtubule dynamics change during the early stages of hypoxia. We demonstrate that microtubule associated protein 4 (MAP4) phosphorylation increases while oncoprotein 18/stathmin (Op18) phosphorylation decreases after hypoxia, but their protein levels do not change. p38/MAPK activity increases quickly after hypoxia concomitant with MAP4 phosphorylation, and the activated p38/MAPK signaling leads to MAP4 phosphorylation and to Op18 dephosphorylation, both of which induce microtubule disruption. We confirmed the interaction between phospho-p38 and MAP4 using immunoprecipitation and found that SB203580, a p38/MAPK inhibitor, increases and MKK6(Glu) overexpression decreases hypoxic cell viability. Our results demonstrate that hypoxia induces microtubule depolymerization and decreased cell viability via the activation of the p38/MAPK signaling pathway and changes the phosphorylation levels of its downstream effectors, MAP4 and Op18.