The regulatory roles of small nucleolar RNAs within their host locus.

Small nucleolar RNAs (snoRNAs) are a class of conserved noncoding RNAs forming complexes with proteins to catalyse site-specific modifications on ribosomal RNA. Besides this canonical role, several snoRNAs are now known to regulate diverse levels of gene expression. While these functions are carried out in trans by mature snoRNAs, evidence has also been emerging of regulatory roles of snoRNAs in cis, either within their genomic locus or as longer transcription intermediates during their maturation. Herein, we review recent findings that snoRNAs can interact in cis with their intron to regulate the expression of their host gene. We also explore the ever-growing diversity of longer host-derived snoRNA extensions and their functional impact across the transcriptome. Finally, we discuss the role of snoRNA duplications into forging these new layers of snoRNA-mediated regulation, as well as their involvement in the genomic imprinting of their host locus.

NRPS-like ATRR in Plant-Parasitic Nematodes Involved in Glycine Betaine Metabolism to Promote Parasitism.

Plant-parasitic nematodes (PPNs) are among the most serious phytopathogens and cause widespread and serious damage in major crops. In this study, using a genome mining method, we identified nonribosomal peptide synthetase (NRPS)-like enzymes in genomes of plant-parasitic nematodes, which are conserved with two consecutive reducing domains at the N-terminus (A-T-R1-R2) and homologous to fungal NRPS-like ATRR. We experimentally investigated the roles of the NRPS-like enzyme (MiATRR) in nematode (Meloidogyne incognita) parasitism. Heterologous expression of Miatrr in Saccharomyces cerevisiae can overcome the growth inhibition caused by high concentrations of glycine betaine. RT-qPCR detection shows that Miatrr is significantly upregulated at the early parasitic life stage (J2s in plants) of M. incognita. Host-derived Miatrr RNA interference (RNAi) in Arabidopsis thaliana can significantly decrease the number of galls and egg masses of M. incognita, as well as retard development and reduce the body size of the nematode. Although exogenous glycine betaine and choline have no obvious impact on the survival of free-living M. incognita J2s (pre-parasitic J2s), they impact the performance of the nematode in planta, especially in Miatrr-RNAi plants. Following application of exogenous glycine betaine and choline in the rhizosphere soil of A. thaliana, the numbers of galls and egg masses were obviously reduced by glycine betaine but increased by choline. Based on the knowledge about the function of fungal NRPS-like ATRR and the roles of glycine betaine in host plants and nematodes, we suggest that MiATRR is involved in nematode-plant interaction by acting as a glycine betaine reductase, converting glycine betaine to choline. This may be a universal strategy in plant-parasitic nematodes utilizing NRPS-like ATRR to promote their parasitism on host plants.

Polymer Beads Increase Field Responses to Host Attractants in the Dengue Vector Aedes aegypti.

This study investigates the efficacy of three different olfactory cues - cyclohexanone, linalool oxide (LO), and 6-methyl-5-heptan-2-one (sulcatone) - in attracting Aedes aegypti, the primary vector of dengue, using BG sentinel traps in a dengue-endemic area (urban Ukunda) in coastal Kenya. Two experiments were conducted. Experiment 1 compared solid formulations of the compounds in polymer beads against liquid formulations with hexane as the solvent. CO2-baited traps served as controls. In Experiment 2, traps were baited with each compound in the polymer beads, commercial BG-Lure, and CO2. Our results indicate that CO2-baited traps recorded the greatest Ae. aegypti captures in both Experiment 1 and 2, whereas trap captures with polymer beads and solvent-based treatments were comparable. In experiment 2, polymer bead-based treatments yielded significantly greater female captures, each recording ~ 2-fold more captures than traps baited with the BG-Lure. There was no significant difference, however, between the treatments. Female Ae. aegypti captured in CO2-baited traps were mainly unfed (91%), with fewer gravid mosquitoes (6.4%) compared to traps with test compounds (range; 12.7-21.1%). Male captures were lower in LO and BG-Lure baited traps compared to other treatments. Gravimetric analysis showed LO had a slower release rate compared to other compounds. The findings suggest that host-associated compounds loaded on polymer beads are more effective in trapping Ae. aegypti than commercial BG-Lure and reveal sex-specific differences in mosquito responses. These results have implications for mosquito surveillance and control programs, highlighting the potential for selective trapping strategies.

In Vitro Profiling of Potential Fish Probiotics, Enterococcus hirae Strains, Isolated from Jade Perch, and Safety Properties Assessed Using Whole Genome Sequencing.

The demands of intensified aquaculture production and escalating disease prevalence underscore the need for efficacious probiotic strategies to enhance fish health. This study focused on isolating and characterising potential probiotics from the gut microbiota of the emerging aquaculture species jade perch (Scortum barcoo). Eighty-seven lactic acid bacteria and 149 other bacteria were isolated from the digestive tract of five adult jade perch. The screening revealed that 24 Enterococcus hirae isolates inhibited the freshwater pathogens Aeromonas sobria and Streptococcus iniae. Co-incubating E. hirae with the host gut suspensions demonstrated a two- to five-fold increase in the size of growth inhibition zones compared to the results when using gut suspensions from tilapia (a non-host), indicating host-specificity. Genome analysis of the lead isolate, E. hirae R44, predicted the presence of antimicrobial compounds like enterolysin A, class II lanthipeptide, and terpenes, which underlay its antibacterial attributes. Isolate R44 exhibited desirable probiotic characteristics, including survival at pH values within the range of 3 to 12, bile tolerance, antioxidant activity, ampicillin sensitivity, and absence of transferable antimicrobial resistance genes and virulence factors commonly associated with hospital Enterococcus strains (IS16, hylEfm, and esp). This study offers a foundation for sourcing host-adapted probiotics from underexplored aquaculture species. Characterisation of novel probiotics like E. hirae R44 can expedite the development of disease mitigation strategies to support aquaculture intensification.

Peroxisome dynamics determines host-derived ROS accumulation and infectious growth of the rice blast fungus.

IMPORTANCE: The interplay between plant and pathogen is a dynamic process, with the host's innate defense mechanisms serving a crucial role in preventing infection. In response to many plant pathogen infections, host cells generate the key regulatory molecule, reactive oxygen species (ROS), to limit the spread of the invading organism. In this study, we reveal the effects of fungal peroxisome dynamics on host ROS homeostasis, during the rice blast fungus Magnaporthe oryzae infection. The elongation of the peroxisome appears contingent upon ROS and links to the accumulation of ROS within the host and the infectious growth of the pathogen. Importantly, we identify a peroxisomal 3-ketoacyl-CoA thiolase, MoKat2, responsible for the elongation of the peroxisome during the infection. In response to host-derived ROS, the homodimer of MoKat2 undergoes dissociation to bind peroxisome membranes for peroxisome elongation. This process, in turn, inhibits the accumulation of host ROS, which is necessary for successful infection. Overall, our study is the first to highlight the intricate relationship between fungal organelle dynamics and ROS-mediated host immunity, extending the fundamental knowledge of pathogen-host interaction.

Utilisation of probiotics for disease management in giant freshwater prawn (Macrobrachium rosenbergii): Administration methods, antagonistic effects and immune response.

The giant freshwater prawn (Macrobrachium rosenbergii) is a high-yielding prawn variety well-received worldwide due to its ability to adapt to freshwater culture systems. Macrobrachium rosenbergii is an alternative to shrimp typically obtained from marine and brackish aquaculture systems. However, the use of intensive culture systems can lead to disease outbreaks, particularly in larval and post-larval stages, caused by pathogenic agents such as viruses, bacteria, fungi, yeasts and protozoans. White tail disease (viral), white spot syndrome (viral) and bacterial necrosis are examples of economically significant diseases. Given the increasing antibiotic resistance of disease-causing microorganisms, probiotics have emerged as promising alternatives for disease control. Probiotics are live active microbes that are introduced into a target host in an adequate number or dose to promote its health. In the present paper, we first discuss the diseases that occur in M. rosenbergii production, followed by an in-depth discussion on probiotics. We elaborate on the common methods of probiotics administration and explain the beneficial health effects of probiotics as immunity enhancers. Moreover, we discuss the antagonistic effects of probiotics on pathogenic microorganisms. Altogether, this paper provides a comprehensive overview of disease control in M. rosenbergii aquaculture through the use of probiotics, which could enhance the sustainability of prawn culture.

Cystic echinococcosis microRNAs as potential noninvasive biomarkers: current insights and upcoming perspective.

INTRODUCTION: Echinococcosis, also known as hydatidosis, is a zoonotic foodborne disease occurred by infection with the larvae of Echinococcus spp. which can lead to the development of hydatid cysts in various organs of the host. The diagnosis of echinococcosis remains challenging due to limited diagnostic tools. AREAS COVERED: In recent years, microRNAs (miRNAs) have emerged as a promising biomarker for various infectious diseases, including those caused by helminths. Recent studies have identified several novel miRNAs in Echinococcus spp. shedding light on their essential roles in hydatid cyst host-parasite interactions. In this regard, several studies have shown that Echinococcus-derived miRNAs are present in biofluids such as serum and plasma of infected hosts. The detection of these miRNAs in the early stages of infection can serve as an early prognostic and diagnostic biomarker for echinococcosis. EXPERT OPINION: The miRNAs specific to Echinococcus spp. show great potential as early diagnostic biomarkers for echinococcosis and can also provide insights into the pathogenesis of this disease. This review attempts to provide a comprehensive overview of Echinococcus-specific miRNAs, their use as early diagnostic biomarkers, and their function in host-parasite interactions.

Host blood-based biosignatures for subclinical TB and incipient TB: A prospective study of adult TB household contacts in Southern India.

A large proportion of the global tuberculosis (TB) burden is asymptomatic and not detectable by symptom-based screening, driving the TB epidemic through continued M. tuberculosis transmission. Currently, no validated tools exist to diagnose incipient and subclinical TB. Nested within a large prospective study in household contacts of pulmonary TB cases in Southern India, we assessed 35 incipient TB and 12 subclinical TB cases, along with corresponding household active TB cases (n=11), and household controls (n=39) using high throughput methods for transcriptional and protein profiling. We split the data into training and test sets and applied a support vector machine classifier followed by a Lasso regression model to identify signatures. The Lasso regression model identified an 11-gene signature (ABLIM2, C20orf197, CTC-543D15.3, CTD-2503O16.3, HLADRB3, METRNL, RAB11B-AS1, RP4-614C10.2, RNA5SP345, RSU1P1, and UACA) that distinguished subclinical TB from incipient TB with a very good discriminatory power by AUCs in both training and test sets. Further, we identified an 8-protein signature comprising b-FGF, IFNγ, IL1RA, IL7, IL12p70, IL13, PDGF-BB, and VEGF that differentiated subclinical TB from incipient TB with good and moderate discriminatory power by AUCs in the training and test sets, respectively. The identified 11-gene signature discriminated well between the distinct stages of the TB disease spectrum, with very good discriminatory power, suggesting it could be useful for predicting TB progression in household contacts. However, the high discriminatory power could partly be due to over-fitting, and validation in other studies is warranted to confirm the potential of the immune biosignatures for identifying subclinical TB.

The interaction of Akkermansia muciniphila with host-derived substances, bacteria and diets.

Trillions of microbes inhabit the human gut and build extremely complex communities. Gut microbes contribute to host metabolisms for better or worse and are widely studied and associated with health and disease. Akkermansia muciniphila is a gut microbiota member, which uses mucin as both carbon and nitrogen sources. Many studies on A. muciniphila have been conducted since this unique bacterium was first described in 2004. A. muciniphila can play an important role in our health because of its beneficial effects, such as improving type II diabetes and obesity and anti-inflammation. A. muciniphila establishes its position as a next-generation probiotic. Besides the effect of A. muciniphila on host health, a technique for boosting has been investigated. In this review, we show what factors can modulate the abundance of A. muciniphila focusing on the interaction with host-derived substances, other bacteria and diets. This review also refers to the possibility of the interaction between medicine and A. muciniphila; this will open up future treatment strategies that can increase A. muciniphila abundance in the gut. KEY POINTS: • Host-derived substances such as bile, microRNA and melatonin as well as mucin have beneficial effects on A. muciniphila. • Gut and probiotic bacteria and diet ingredients such as carbohydrates and phytochemicals could boost the abundance of A. muciniphila. • Several medicines could affect the growth of A. muciniphila.

Predictive Periodontitis: The Most Promising Salivary Biomarkers for Early Diagnosis of Periodontitis.

The primary cause of tooth loss in the industrialized world is periodontitis, a bacterial anaerobic infection whose pathogenesis is characterized by composite immune response. At present, the diagnose of periodontitis is made by a complete status check of the patient's periodontal health; full-mouth plaque score, full-mouth bleeding score, probing depth, clinical attachment level, bleeding on probing, recessions, mobility, and migration are evaluated in order to provides a clear picture of the periodontal conditions of a single patient. Chair-side diagnostic tests based on whole saliva could be routinely used by periodontists for a very early diagnosis of periodontitis, monitoring, prognosis, and management of periodontal patients by biomarker detection, whose diagnostic validity is related to sensitivity and specificity. Recent paper reviews and meta-analyses have focused on five promising host derived biomarkers as candidate for early diagnosis of periodontitis: MMP-8 (Metalloproteinase-8), MIP-1α (Macrophage inflammatory protein-1 alpha), IL-1 ß (Interleukin-1 beta), IL-6 (Interleukin-6), and HB (Hemoglobin), and their combinations. Chair-side Lab-on-a-chip (LOC) technology may soon become an important part of efforts to detect such biomarkers in saliva medium to improve worldwide periodontal health in developed nations as well as in underserved communities and poor countries. Their applications in preventive and predictive medicine is now fundamental, and is aimed at the early detection of risk factors or the presence or evolution of the disease, and in personalized medicine, which aims to identify tailor-made treatments for individual patients. The aim of the present paper is to be informative about host derived periodontal biomarkers and, in particular, we intend to report information about the most important immune response derived biomarkers and Hemoglobin as candidates to be routinely utilized in order to obtain a chair-side early diagnosis of periodontal disease.

Fungal Endophytes as Efficient Sources of Plant-Derived Bioactive Compounds and Their Prospective Applications in Natural Product Drug Discovery: Insights, Avenues, and Challenges.

Fungal endophytes are well-established sources of biologically active natural compounds with many producing pharmacologically valuable specific plant-derived products. This review details typical plant-derived medicinal compounds of several classes, including alkaloids, coumarins, flavonoids, glycosides, lignans, phenylpropanoids, quinones, saponins, terpenoids, and xanthones that are produced by endophytic fungi. This review covers the studies carried out since the first report of taxol biosynthesis by endophytic Taxomyces andreanae in 1993 up to mid-2020. The article also highlights the prospects of endophyte-dependent biosynthesis of such plant-derived pharmacologically active compounds and the bottlenecks in the commercialization of this novel approach in the area of drug discovery. After recent updates in the field of 'omics' and 'one strain many compounds' (OSMAC) approach, fungal endophytes have emerged as strong unconventional source of such prized products.

The Bifidogenic Effect Revisited-Ecology and Health Perspectives of Bifidobacterial Colonization in Early Life.

Extensive microbial colonization of the infant gastrointestinal tract starts after parturition. There are several parallel mechanisms by which early life microbiome acquisition may proceed, including early exposure to maternal vaginal and fecal microbiota, transmission of skin associated microbes, and ingestion of microorganisms present in breast milk. The crucial role of vertical transmission from the maternal microbial reservoir during vaginal delivery is supported by the shared microbial strains observed among mothers and their babies and the distinctly different gut microbiome composition of caesarean-section born infants. The healthy infant colon is often dominated by members of the keystone genus Bifidobacterium that have evolved complex genetic pathways to metabolize different glycans present in human milk. In exchange for these host-derived nutrients, bifidobacteria's saccharolytic activity results in an anaerobic and acidic gut environment that is protective against enteropathogenic infection. Interference with early-life microbiota acquisition and development could result in adverse health outcomes. Compromised microbiota development, often characterized by decreased abundance of Bifidobacterium species has been reported in infants delivered prematurely, delivered by caesarean section, early life antibiotic exposure and in the case of early life allergies. Various microbiome modulation strategies such as probiotic, prebiotics, synbiotics and postbiotics have been developed that are able to generate a bifidogenic shift and help to restore the microbiota development. This review explores the evolutionary ecology of early-life type Bifidobacterium strains and their symbiotic relationship with humans and discusses examples of compromised microbiota development in which stimulating the abundance and activity of Bifidobacterium has demonstrated beneficial associations with health.

Targeted Amino Acid Substitution Overcomes Scale-Up Challenges with the Human C5a-Derived Decapeptide Immunostimulant EP67.

EP67 is a second-generation, human C5a-derived decapeptide agonist of C5a receptor 1 (C5aR1/CD88) that selectively activates mononuclear phagocytes over neutrophils to potentiate protective innate and adaptive immune responses while potentially minimizing neutrophil-mediated toxicity. Pro7 and N-methyl-Leu8 (Me-Leu8) amino acid residues within EP67 likely induce backbone structural changes that increase potency and selective activation of mononuclear phagocytes over neutrophils versus first-generation EP54. The low coupling efficiency between Pro7 and Me-Leu8 and challenging purification by HPLC, however, greatly increase scale-up costs of EP67 for clinical use. Thus, the goal of this study was to determine whether replacing Pro7 and/or Me-Leu8 with large-scale amenable amino acid residues predicted to induce similar structural changes (cyclohexylalanine7 and/or leucine8) sufficiently preserves EP67 activity in primary human mononuclear phagocytes and neutrophils. We found that EP67 analogues had similar potency, efficacy, and selective activation of mononuclear phagocytes over neutrophils. Thus, replacing Pro7 and/or Me-Leu8 with large-scale amenable amino acid residues predicted to induce similar structural changes is a suitable strategy to overcome scale-up challenges with EP67.

Corrigendum: Screening of Host Specific Lactic Acid Bacteria Active Against Escherichia coli From Massive Sample Pools With a Combination of in vitro and ex vivo Methods.

[This corrects the article DOI: 10.3389/fmicb.2019.02705.].

State-of-the-art in host-derived biomarkers of Chagas disease prognosis and early evaluation of anti-Trypanosoma cruzi treatment response.

Chagas disease is caused by infection with the parasite Trypanosoma cruzi, which might lead to a chronic disease state and drive to irreversible damage to the heart and/or digestive tract tissues. Endemic in 21 countries in the Americas, it is the neglected disease with a highest burden in the region. Current estimates point at ~6 million people infected, of which ~30% will progress onto the symptomatic tissue disruptive stage. There is no vaccine but there are two anti-parasitic drugs available: benznidazole and nifurtimox. However, their efficacy is variable at the chronic symptomatic stage and both have frequent adverse effects. Since there are no prognosis markers, drugs should be administered to all T. cruzi-infected individuals in the indeterminate and early symptomatic stages. Nowadays, there are no tests-of-cure either, which greatly undermines patients follow-up and the search of safer and more efficacious drugs. Therefore, the identification and validation of biomarkers of disease progression and/or treatment response on which to develop tests of prognosis and/or cure is a major research priority. Both parasite- and host-derived markers have been investigated. In the present manuscript we present an updated outlook of the latter.

The transcriptional regulator IscR integrates host-derived nitrosative stress and iron starvation in activation of the vvhBA operon in Vibrio vulnificus.

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter P vvhBA , which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of P vvhBA , whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the P vvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of P vvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.

Putative host-derived growth factors inducing colonization of Burkholderia gut symbiont in Riptortus pedestris insect.

It is questionable that how gut symbiont can be proliferated in the host symbiotic organs, such as host midgut region, which are known to be highly stressful and nutritional depleted conditions. Since Riptortus-Burkholderia symbiosis system is a good model to study this question, we hypothesized that Burkholderia symbiont will use host-derived bacterial growth factor(s) to colonize persistently in the host midgut 4 (M4) region, which is known as symbiotic organ. In this study, we observed that although gut-colonized symbiotic Burkholderia cells did not grow in the nutrient-limited media conditions, these symbionts were able to grow dose-dependent manner by addition of host naïve M4 lysate, supporting that host-derived growth factor molecule(s) may exist in the host M4 lysate. By further experiments, a host-derived growth factor(s) did not lose its biological activity in the conditions of high temperature, treatment of phenol-chloroform or ethyl alcohol precipitation, indicating that a growth factor molecule(s) is neither a protein nor a DNA. Also, based on the biochemical analyses data, molecular weight of the host-derived bacterial growth factor(s) was turned out to be less than 3 kDa molecular mass and to give the positive chemical response to the ninhydrin reagent on thin layer chromatography. Finally, we found that one specific peak showing ninhydrin positive signal was separated by gel filtration column and induced proliferative activity for Burkholderia gut symbiont cells.

Biomarkers of Infection and Sepsis.

The role of biomarkers for detection of sepsis has come a long way. Molecular biomarkers are taking front stage at present, but machine learning and other computational measures using bigdata sets are promising. Clinical research in sepsis is hampered by lack of specificity of the diagnosis; sepsis is a syndrome with no uniformly agreed definition. This lack of diagnostic precision means there is no gold standard for this diagnosis. The final conclusion is expert opinion, which is not bad but not perfect. Perhaps machine learning will displace expert opinion as the final and most accurate definition for sepsis.

Screening of Host Specific Lactic Acid Bacteria Active Against Escherichia coli From Massive Sample Pools With a Combination of in vitro and ex vivo Methods.

A novel three-step combination of in vitro and ex vivo screening was established to massively screen host derived lactic acid bacteria (LAB) from the broiler chicken intestine with inhibitory activity against Escherichia coli. In a first step, a massive sample pool consisting of 7102 broiler-derived colonies from intestinal contents were established and sub-cultured. Supernatants thereof were incubated with an E. coli model strain to screen suitable isolates with inhibitory activity. A total of 76 isolates of interest were subsequently further studied based on either pH dependent or -independent activity in the second step of the assay. Here, in-depth growth inhibition of the E. coli model strain and the potential of isolates for lactic acid production as inhibitory substance were indexed for all isolates. Resulting scatter plots of both parameters revealed five isolates with exceptional inhibitory activity that were further studied under ex vivo condition in the third step of the assay. These isolates were taxonomically classified as strains of the species Lactobacillus agilis, Lactobacillus salivarius, and Pediococcus acidilactici. Samples from the broiler chicken intestine were inoculated with the Lactobacillus isolates and the E. coli model strain. After 8 and 24 h incubation, respectively, growth of the E. coli model strain was monitored by cultivation of the E. coli strain in antibiotic supplemented medium. By their superior inhibitory activity against the E. coli model strain, one L. agilis and one L. salivarius strain were selected and characterized for further application as probiotics in broiler chicken. Additionally, their antibiotic resistance patterns and resilience under gastric stress of isolates were also characterized. The results of this study demonstrate that the novel isolation procedure was able to efficiently and rapidly isolate and identify bacterial strains from a massive sample pool with inhibitory potential against specific types of bacteria (here E. coli). The introduction of the final ex vivo selection step additionally confirmed the inhibitory activity of the strains under conditions simulating the intestinal tract of the host. Furthermore, this method revealed a general potential for the isolation of antagonistic strains that active against other pathogenic bacteria with specific biomarker.

Host- and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development.

Extracellular vesicles (EVs) are blebs of either plasma membrane or intracellular membranes carrying a cargo of proteins, nucleic acids, and lipids. EVs are produced by eukaryotic cells both under physiological and pathological conditions. Genetic and environmental factors (diet, stress, etc.) affecting EV cargo, regulating EV release, and consequences on immunity will be covered. EVs are found in virtually all body fluids such as plasma, saliva, amniotic fluid, and breast milk, suggesting key roles in immune development and function at different life stages from in utero to aging. These will be reviewed here. Under pathological conditions, plasma EV levels are increased and exacerbate immune activation and inflammatory reaction. Sources of EV, cells targeted, and consequences on immune function and disease development will be discussed. Both pathogenic and commensal bacteria release EV, which are classified as outer membrane vesicles when released by Gram-negative bacteria or as membrane vesicles when released by Gram-positive bacteria. Bacteria derived EVs can affect host immunity with pathogenic bacteria derived EVs having pro-inflammatory effects of host immune cells while probiotic derived EVs mostly shape the immune response towards tolerance.