Effector-Triggered Immunity.

The innate immune system detects pathogens via germline-encoded receptors that bind to conserved pathogen ligands called pathogen-associated molecular patterns (PAMPs). Here we consider an additional strategy of pathogen sensing called effector-triggered immunity (ETI). ETI involves detection of pathogen-encoded virulence factors, also called effectors. Pathogens produce effectors to manipulate hosts to create a replicative niche and/or block host immunity. Unlike PAMPs, effectors are often diverse and rapidly evolving and can thus be unsuitable targets for direct detection by germline-encoded receptors. Effectors are instead often sensed indirectly via detection of their virulence activities. ETI is a viable strategy for pathogen sensing and is used across diverse phyla, including plants, but the molecular mechanisms of ETI are complex compared to simple receptor/ligand-based PAMP detection. Here we survey the mechanisms and functions of ETI, with a particular focus on emerging insights from animal studies. We suggest that many examples of ETI may remain to be discovered, hiding in plain sight throughout immunology.

Six distinct NFκB signaling codons convey discrete information to distinguish stimuli and enable appropriate macrophage responses.

Macrophages initiate inflammatory responses via the transcription factor NFκB. The temporal pattern of NFκB activity determines which genes are expressed and thus, the type of response that ensues. Here, we examined how information about the stimulus is encoded in the dynamics of NFκB activity. We generated an mVenus-RelA reporter mouse line to enable high-throughput live-cell analysis of primary macrophages responding to host- and pathogen-derived stimuli. An information-theoretic workflow identified six dynamical features-termed signaling codons-that convey stimulus information to the nucleus. In particular, oscillatory trajectories were a hallmark of responses to cytokine but not pathogen-derived stimuli. Single-cell imaging and RNA sequencing of macrophages from a mouse model of Sjögren's syndrome revealed inappropriate responses to stimuli, suggestive of confusion of two NFκB signaling codons. Thus, the dynamics of NFκB signaling classify immune threats through six signaling codons, and signal confusion based on defective codon deployment may underlie the etiology of some inflammatory diseases.

Human IFIT3 Modulates IFIT1 RNA Binding Specificity and Protein Stability.

Although interferon-induced proteins with tetratricopeptide repeats (IFIT proteins) inhibit infection of many viruses by recognizing their RNA, the regulatory mechanisms involved remain unclear. Here we report a crystal structure of cap 0 (m7GpppN) RNA bound to human IFIT1 in complex with the C-terminal domain of human IFIT3. Structural, biochemical, and genetic studies suggest that IFIT3 binding to IFIT1 has dual regulatory functions: (1) extending the half-life of IFIT1 and thereby increasing its steady-state amounts in cells; and (2) allosterically regulating the IFIT1 RNA-binding channel, thereby enhancing the specificity of recognition for cap 0 but not cap 1 (m7GpppNm) or 5'-ppp RNA. Mouse Ifit3 lacks this key C-terminal domain and does not bind mouse Ifit1. The IFIT3 interaction with IFIT1 is important for restricting infection of viruses lacking 2'-O methylation in their RNA cap structures. Our experiments establish differences in the regulation of IFIT1 orthologs and define targets for modulation of human IFIT protein activity.

Immune profiling reveals umbilical cord blood mononuclear cells from South India display an IL-8 dominant, CXCL-10 deficient polyfunctional monocyte response to pathogen-associated molecular patterns (PAMPs) that is distinct from adult blood cells.

Neonate responses to pathogen-associated molecular patterns (PAMPS) differ from adults; such understanding is poor in Indian neonates, despite recognised significant infectious risk. Immune profiling analysis was undertaken of ten secreted mediators contextualised with cellular source induced by six PAMPs in umbilical cord (CB; n=21) and adult-blood (PBMC, n=14) from a tertiary care hospital in South India. Differential cytokine expression analysis (minimum log2-fold difference; adj p-value<0.05) identified bacterial PAMPs induced higher concentrations of IL-1ß, IL-10, TNF-α in adults versus IL-8, GM-CSF, IFN-γ and IL-2 in CB. CB responded to poly I:C and SARS-CoV-2 lysate with a dominant IL-8 response, whereas, in PBMC, CXCL-10 dominated poly I:C, but not SARS-CoV-2, responses, highlighting potential IL-8 importance, in absence of Type I Interferons, in antiviral CB immunity. Candida albicans was the only PAMP to uniformly induce higher secretion of effectors in CB. The predominant source of IL-8/IL-6/TNF-α/IL-1ß in both CB and PBMC was polyfunctional monocytes and IFN-γ /IL-2/IL-17 from innate lymphocytes. Correlation matrix analyses revealed IL-8 to be the most differentially regulated, correlating positively in CB versus negatively in PBMC with IL-6, GM-CSF, IFN-γ, IL-2, consistent with more negatively regulated cytokine modules in adults, potentially linked to higher anti-inflammatory IL-10. Cord and adult blood from India respond robustly to PAMPs with unique effector combinations. These data provide a strong foundation to monitor, explore, mechanisms that regulate such immunity during the life course, an area of significant global health importance given infection-related infant mortality incidence.

The phagocytosis oxidase/Bem1p domain-containing protein PB1CP negatively regulates the NADPH oxidase RBOHD in plant immunity.

Perception of pathogen-associated molecular patterns (PAMPs) by surface-localized pattern recognition receptors activates RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD) through direct phosphorylation by BOTRYTIS-INDUCED KINASE 1 (BIK1) and induces the production of reactive oxygen species (ROS). RBOHD activity must be tightly controlled to avoid the detrimental effects of ROS, but little is known about RBOHD downregulation. To understand the regulation of RBOHD, we used co-immunoprecipitation of RBOHD with mass spectrometry analysis and identified PHAGOCYTOSIS OXIDASE/BEM1P (PB1) DOMAIN-CONTAINING PROTEIN (PB1CP). PB1CP negatively regulates RBOHD and the resistance against the fungal pathogen Colletotrichum higginsianum. PB1CP competes with BIK1 for binding to RBOHD in vitro. Furthermore, PAMP treatment enhances the PB1CP-RBOHD interaction, thereby leading to the dissociation of phosphorylated BIK1 from RBOHD in vivo. PB1CP localizes at the cell periphery and PAMP treatment induces relocalization of PB1CP and RBOHD to the same small endomembrane compartments. Additionally, overexpression of PB1CP in Arabidopsis leads to a reduction in the abundance of RBOHD protein, suggesting the possible involvement of PB1CP in RBOHD endocytosis. We found PB1CP, a novel negative regulator of RBOHD, and revealed its possible regulatory mechanisms involving the removal of phosphorylated BIK1 from RBOHD and the promotion of RBOHD endocytosis.

Primate innate immune responses to bacterial and viral pathogens reveals an evolutionary trade-off between strength and specificity.

Despite their close genetic relatedness, apes and African and Asian monkeys (AAMs) differ in their susceptibility to severe bacterial and viral infections that are important causes of human disease. Such differences between humans and other primates are thought to be a result, at least in part, of interspecies differences in immune response to infection. However, because of the lack of comparative functional data across species, it remains unclear in what ways the immune systems of humans and other primates differ. Here, we report the whole-genome transcriptomic responses of ape species (human and chimpanzee) and AAMs (rhesus macaque and baboon) to bacterial and viral stimulation. We find stark differences in the responsiveness of these groups, with apes mounting a markedly stronger early transcriptional response to both viral and bacterial stimulation, altering the transcription of ∼40% more genes than AAMs. Additionally, we find that genes involved in the regulation of inflammatory and interferon responses show the most divergent early transcriptional responses across primates and that this divergence is attenuated over time. Finally, we find that relative to AAMs, apes engage a much less specific immune response to different classes of pathogens during the early hours of infection, up-regulating genes typical of anti-viral and anti-bacterial responses regardless of the nature of the stimulus. Overall, these findings suggest apes exhibit increased sensitivity to bacterial and viral immune stimulation, activating a broader array of defense molecules that may be beneficial for early pathogen killing at the potential cost of increased energy expenditure and tissue damage.

Pyroptotic and non-pyroptotic effector functions of caspase-11.

Innate immune cells, epithelial cells, and many other cell types are capable of detecting infection or tissue injury, thus mounting regulated immune response. Inflammasomes are highly sophisticated and effective orchestrators of innate immunity. These oligomerized multiprotein complexes are at the center of various innate immune pathways, including modulation of the cytoskeleton, production and maturation of cytokines, and control of bacterial growth and cell death. Inflammasome assembly often results in caspase-1 activation, which is an inflammatory caspase that is involved in pyroptotic cell death and release of inflammatory cytokines in response to pathogen patterns and endogenous danger stimuli. However, the nature of stimuli and inflammasome components are diverse. Caspase-1 activation mediated release of mature IL-1ß and IL-18 in response to canonical stimuli initiated by NOD-like receptor (NLR), and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). On the other hand, caspase-11 delineates a non-canonical inflammasome that promotes pyroptotic cell death and non-pyroptotic functions in response to non-canonical stimuli. Caspase-11 in mice and its homologues in humans (caspase-4/5) belong to caspase-1 family of cysteine proteases, and play a role in inflammation. Knockout mice provided new genetic tools to study inflammatory caspases and revealed the role of caspase-11 in mediating septic shock in response to lethal doses of lipopolysaccharide (LPS). Recognition of LPS mediates caspase-11 activation, which promotes a myriad of downstream effects that include pyroptotic and non-pyroptotic effector functions. Therefore, the physiological functions of caspase-11 are much broader than its previously established roles in apoptosis and cytokine maturation. Inflammation induced by exogenous or endogenous agents can be detrimental and, if excessive, can result in organ and tissue damage. Consequently, the existence of sophisticated mechanisms that tightly regulate the specificity and sensitivity of inflammasome pathways provides a fine-tuning balance between adequate immune response and minimal tissue damage. In this review, we summarize effector functions of caspase-11.

Treatment of Bacterial Infections with ß-Lactams: Cooperation with Innate Immunity.

ß-Lactams are the most widely prescribed antibiotics used for the control and treatment of bacterial infections. The direct effect of ß-lactams on bacteria is well studied worldwide. In the context of infections and as a consequence of their direct activity against the pathogen, ß-lactams also regulate antibacterial immune responses. This knowledge has led to the theorem that the effectiveness of ß-lactam treatment results from the synergy between the drug and the immune response. Key players in this immune response, with an essential role in the clearance of live and dead bacteria, are the myeloid cells. In this review, we summarize the data that shed light on how ß-lactams interact with myeloid cells during bacterial infection treatment.

Cyclophilin effector Al106 of mirid bug Apolygus lucorum inhibits plant immunity and promotes insect feeding by targeting PUB33.

Apolygus lucorum (Meyer-Dur; Heteroptera: Miridae) is a major agricultural pest infesting crops, vegetables, and fruit trees. During feeding, A. lucorum secretes a plethora of effectors into its hosts to promote infestation. However, the molecular mechanisms of these effectors manipulating plant immunity are largely unknown. Here, we investigated the molecular mechanism underlying the effector Al106 manipulation of plant-insect interaction by RNA interference, electrical penetration graph, insect and pathogen bioassays, protein-protein interaction studies, and protein ubiquitination experiment. Expression of Al106 in Nicotiana benthamiana inhibits pathogen-associated molecular pattern-induced cell death and reactive oxygen species burst, and promotes insect feeding and plant pathogen infection. In addition, peptidyl-prolyl cis-trans isomerase (PPIase) activity of Al106 is required for its function to inhibit PTI.Al106 interacts with a plant U-box (PUB) protein, PUB33, from N. benthamiana and Arabidopsis thaliana. We also demonstrated that PUB33 is a positive regulator of plant immunity. Furthermore, an in vivo assay revealed that Al106 inhibits ubiquitination of NbPUB33 depending on PPIase activity. Our findings revealed that a novel cyclophilin effector may interact with plant PUB33 to suppress plant immunity and facilitate insect feeding in a PPIase activity-dependent manner.

Resolving intergenotypic Striga resistance in sorghum.

Genetic underpinnings of host-pathogen interactions in the parasitic plant Striga hermonthica, a root parasitic plant that ravages cereals in sub-Saharan Africa, are unclear. We performed a comparative transcriptome study on five genotypes of sorghum exhibiting diverse resistance responses to S. hermonthica using weighted gene co-expression network analysis (WGCNA). We found that S. hermonthica elicits both basal and effector-triggered immunity-like a bona fide pathogen. The resistance response was genotype specific. Some resistance responses followed the salicylic acid-dependent signaling pathway for systemic acquired resistance characterized by cell wall reinforcements, lignification, and callose deposition, while in others the WRKY-dependent signaling pathway was activated, leading to a hypersensitive response. In some genotypes, both modes of resistance were activated, while in others either mode dominated the resistance response. Cell wall-based resistance was common to all sorghum genotypes but strongest in IS2814, while a hypersensitive response was specific to N13, IS9830, and IS41724. WGCNA further allowed for pinpointing of S. hermonthica resistance causative genes in sorghum, including glucan synthase-like 10 gene, a pathogenesis-related thaumatin-like family gene, and a phosphoinositide phosphatase gene. Such candidate genes will form a good basis for subsequent functional validation and possibly future resistance breeding.

Genome-wide identification of gap junction (connexins and pannexins) genes in black rockfish (Sebastes schlegelii): Evolution and immune response mechanism following challenge.

Cell-to-cell communication through gap junction channels is very important to coordinate the functions of cells in all multicellular biological tissues. It allows the direct exchange of ions and small molecules (including second messengers, such as Ca2+, IP3, cyclic nucleotides, and oligonucleotides). In this study, a total of 48 members of the gap junction (GJ) protein family were identified from Sebastes schlegelii. In S. schlegelii, GJ proteins were classified into two types, connexin, and pannexin, and then connexins were divided into five subfamilies. The naming of 48 genes was verified through phylogenetic analysis and syntenic analysis. The connexin proteins contained four transmembrane fragments and two extracellular loops, the lengths of the intracellular loop and C-terminal was quite different, and the C-terminal region was highly variable after post-translational modification. PPI analysis showed that GJs interacted with tight junctions, adhesive junctions, and cell adhesions to form a complex network and participated in cell-cell junction organization, ATP binding, ion channel, voltage-gated conduction, wnt signaling pathway, Fc-γ receptor signaling pathway, and DNA replication. In addition, the S. schlegelii GJ protein was highly expressed in intestinal tissues and remarkably regulated after Edwardsiella tarda and Streptococcus iniae infection. The expression of GJs in intestinal cells of S. schlegelii was significantly regulated by LPS and poly (I:C), which was consistent with the results of intestinal tissue stimulation by pathogens. In conclusion, this study can provide valuable information for further research on the function of S. schlegelii GJ proteins.

In-vivo analysis of Protec™ and ß-glucan supplementation on innate immune performance and intestinal health of rainbow trout.

Functional diets are often given to fish during key stages to improve health through the interaction of the feed components with the host intestine. The additional factors added in these diets are known to modulate the immune response and as such may also offer protection against pathogenic challenges. The present study was undertaken to evaluate whether ß-glucan supplementation for 6 weeks can alter the magnitude of immune response to immunological challenges and subsequently offer an improved innate immune response to bacterial challenge in rainbow trout. Two experimental diets were used to study these effects: a basic commercial diet supplemented with ß-glucan and a commercially available functional diet (Protec™) that has ß-glucan as a functional component in addition to other components were compared to a basic commercial control diet. No significant differences were observed in biometric data. Histological analysis revealed a significantly greater number of goblet cells in the fish fed Protec™ and ß-glucan diets compared to those fed a control diet. Cell marker gene expression of distal intestine leucocytes indicated higher expression of T- and B-cells marker genes to both the ß-glucan containing diets in comparison to control. The Protec™ diet demonstrated modulation of innate immune markers after 6 weeks of feeding with key antimicrobial genes (SAA, HAMP, IL-1ß and TNFα) showing significant increases compared to the other diets. After stimulation with both PAMPs and an immune challenge with A. salmonicida fish fed the ß-glucan diet and the Protec™ exhibited modulation of the innate immune response. An immune challenge with A. salmonicida was carried out to identify if dietary composition led to differences in the innate immune response of rainbow trout. Modulation of the magnitude of response in some immune genes (SAA, IL-1ß and HAMP) was observed in both the distal intestine and head kidney in the Protec™ and ß-glucan fed fish compared to those fed the control diet.

Innate Immune Responses to Sporothrix schenckii: Recognition and Elimination.

Sporothrix schenckii (S. schenckii), a ubiquitous thermally dimorphic fungus, is the etiological agent of sporotrichosis, affecting immunocompromised and immunocompetent individuals. Despite current antifungal regimens, sporotrichosis results in prolonged treatment and significant mortality rates in the immunosuppressed population. The innate immune system forms the host's first and primary line of defense against S. schenckii, which has a bi-layered cell wall structure. Many components act as pathogen-associated molecular patterns (PAMPs) in pathogen-host interactions. PAMPs are recognized by pattern recognition receptors (PRRs) such as toll-like receptors, C-type lectin receptors, and complement receptors, triggering innate immune cells such as neutrophils, macrophages, and dendritic cells to phagocytize or produce mediators, contributing to S. schenckii elimination. The ultrastructure of S. schenckii and pathogen-host interactions, including PRRs and innate immune cells, are summarized in this review, promoting a better understanding of the innate immune response to S. schenckii and aiding in the development of protective and therapeutic strategies to combat sporotrichosis.

Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder.

Patients who have recovered from coronavirus disease 2019 (COVID-19) infection may experience chronic fatigue when exercising, despite no obvious heart or lung abnormalities. The present lack of effective treatments makes managing long COVID a major challenge. One of the underlying mechanisms of long COVID may be mitochondrial dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can alter the mitochondria responsible for energy production in cells. This alteration leads to mitochondrial dysfunction which, in turn, increases oxidative stress. Ultimately, this results in a loss of mitochondrial integrity and cell death. Moreover, viral proteins can bind to mitochondrial complexes, disrupting mitochondrial function and causing the immune cells to over-react. This over-reaction leads to inflammation and potentially long COVID symptoms. It is important to note that the roles of mitochondrial damage and inflammatory responses caused by SARS-CoV-2 in the development of long COVID are still being elucidated. Targeting mitochondrial function may provide promising new clinical approaches for long-COVID patients; however, further studies are needed to evaluate the safety and efficacy of such approaches.

The Heterogeneous Landscape and Early Evolution of Pathogen-Associated CpG Dinucleotides in SARS-CoV-2.

COVID-19 can lead to acute respiratory syndrome, which can be due to dysregulated immune signaling. We analyze the distribution of CpG dinucleotides, a pathogen-associated molecular pattern, in the SARS-CoV-2 genome. We characterize CpG content by a CpG force that accounts for statistical constraints acting on the genome at the nucleotidic and amino acid levels. The CpG force, as the CpG content, is overall low compared with other pathogenic betacoronaviruses; however, it widely fluctuates along the genome, with a particularly low value, comparable with the circulating seasonal HKU1, in the spike coding region and a greater value, comparable with SARS and MERS, in the highly expressed nucleocapside coding region (N ORF), whose transcripts are relatively abundant in the cytoplasm of infected cells and present in the 3'UTRs of all subgenomic RNA. This dual nature of CpG content could confer to SARS-CoV-2 the ability to avoid triggering pattern recognition receptors upon entry, while eliciting a stronger response during replication. We then investigate the evolution of synonymous mutations since the outbreak of the COVID-19 pandemic, finding a signature of CpG loss in regions with a greater CpG force. Sequence motifs preceding the CpG-loss-associated loci in the N ORF match recently identified binding patterns of the zinc finger antiviral protein. Using a model of the viral gene evolution under human host pressure, we find that synonymous mutations seem driven in the SARS-CoV-2 genome, and particularly in the N ORF, by the viral codon bias, the transition-transversion bias, and the pressure to lower CpG content.

Microbial pathogens induce neurodegeneration in Alzheimer's disease mice: protection by microglial regulation.

BACKGROUND: Neurodegeneration is considered the consequence of misfolded proteins' deposition. Little is known about external environmental effects on the neurodegenerative process. Infectious agent-derived pathogen-associated molecular patterns (PAMPs) activate microglia, key players in neurodegenerative diseases. We hypothesized that systemic microbial pathogens may accelerate neurodegeneration in Alzheimer's disease (AD) and that microglia play a central role in this process. METHODS: We examined the effect of an infectious environment and of microbial Toll-like receptor (TLR) agonists on cortical neuronal loss and on microglial phenotype in wild type versus 5xFAD transgenic mice, carrying mutated genes associated with familial AD. RESULTS: We examined the effect of a naturally bred environment on the neurodegenerative process. Earlier and accelerated cortical neuron loss occurred in 5xFAD mice housed in a natural ("dirty") environment than in a specific-pathogen-free (SPF) environment, without increasing the burden of Amyloid deposits and microgliosis. Neuronal loss occurred in a microglia-rich cortical region but not in microglia-poor CA regions of the hippocampus. Environmental exposure had no effect on cortical neuron density in wild-type mice. To model the neurodegenerative process caused by the natural infectious environment, we injected systemically the bacterial endotoxin lipopolysaccharide (LPS), a TLR4 agonist PAMP. LPS caused cortical neuronal death in 5xFAD, but not wt mice. We used the selective retinoic acid receptor α agonist Am580 to regulate microglial activation. In primary microglia isolated from 5xFAD mice, Am580 markedly attenuated TLR agonists-induced iNOS expression, without canceling their basic immune response. Intracerebroventricular delivery of Am580 in 5xFAD mice reduced significantly the fraction of (neurotoxic) iNOS + microglia and increased the fraction of (neuroprotective) TREM2 + microglia. Furthermore, intracerebroventricular delivery of Am580 prevented neurodegeneration induced by microbial TLR agonists. CONCLUSIONS: Exposure to systemic infections causes neurodegeneration in brain regions displaying amyloid pathology and high local microglia density. AD brains exhibit increased susceptibility to microbial PAMPs' neurotoxicity, which accelerates neuronal death. Microglial modulation protects the brain from microbial TLR agonist PAMP-induced neurodegeneration.

Gut microbiota and bone metabolism.

Osteoporosis is the most common metabolic skeletal disease. It is characterized by the deterioration of the skeletal microarchitecture and bone loss, leading to ostealgia, and even bone fractures. Accumulating evidence has indicated that there is an inextricable relationship between the gut microbiota (GM) and bone homeostasis involving host-microbiota crosstalk. Any perturbation of the GM can play an initiating and reinforcing role in disrupting the bone remodeling balance during the development of osteoporosis. Although the GM is known to influence bone metabolism, the mechanisms associated with these effects remain unclear. Herein, we review the current knowledge of how the GM affects bone metabolism in health and disease, summarize the correlation between pathogen-associated molecular patterns of GM structural components and bone metabolism, and discuss the potential mechanisms underlying how GM metabolites regulate bone turnover. Deciphering the complicated relationship between the GM and bone health will provide new insights into the prevention and treatment of osteoporosis.

Activation mechanisms of inflammasomes by bacterial toxins.

Inflammasomes are cytosolic innate immune complexes, which assemble in mammalian cells in response to microbial components and endogenous danger signals. A major family of inflammasome activators is bacterial toxins. Inflammasome sensor proteins, such as the nucleotide-binding oligomerisation domain-like receptor (NLR) family members NLRP1b and NLRP3, and the tripartite motif family member Pyrin+ efflux triggered by pore-forming toxins or by other toxin-induced homeostasis-altering events such as lysosomal rupture. Pyrin senses perturbation of host cell functions induced by certain enzymatic toxins resulting in impairment of RhoA GTPase activity. Assembly of the inflammasome complex activates the cysteine protease caspase-1, leading to the proteolytic cleavage of the proinflammatory cytokines IL-1ß and IL-18, and the pore-forming protein gasdermin D causing pyroptosis. In this review, we discuss the latest progress in our understanding on the activation mechanisms of inflammasome complexes by bacterial toxins and effector proteins and explore avenues for future research into the relationships between inflammasomes and bacterial toxins.

Distribution of flagellin CD2-1, flg22, and flgII-28 recognition systems in plant species and regulation of plant immune responses through these recognition systems.

The first layer of active plant immunity relies upon the recognition of pathogen-associated molecular patterns (PAMPs), and the induction of PTI. Flagellin is the major protein component of the bacterial flagellum. Flagellin-derived peptide fragments such as CD2-1, flg22, and flgII-28 function as PAMPs in most higher plants. To determine the distribution of CD2-1, flg22, and flgII-28 recognition systems within plant species, the inducibility of PTI by CD2-1, flg22, and flgII-28 in 8 plant species, including monocotyledonous and dicotyledonous plants, was investigated. CD2-1 caused PTI responses in Oryza sativa, Brachypodium distachyon, and Asparagus persicus; flg22 caused PTI responses in Phyllostachys nigra, A. persicus, Arabidopsis thaliana, Nicotiana tabacum, Solanum lycopersicum, and Lotus japonicus; and flgII-28 caused PTI responses only in S. lycopersicum. Furthermore, quantitative analysis of FLS2 receptor revealed that the responsiveness of flg22 in plants was dependent on the expression level of the receptor.

Innate Immunity and Phenoptosis.

The hypothesis is proposed that activation of innate immunity is the primary mechanism of phenoptosis (programmed death of an organism). In support of the hypothesis, we discuss (i) the data on active release of signaling molecules from the cell producing excessive inflammation; (ii) the data on contribution of mitochondrial production of reactive oxygen species to immune response.