Immune Defense System Research Articles

Cytotoxic and chemotactic dynamics of NK cells quantified by live-cell imaging.

Natural Killer (NK) cells detect and eliminate virus-infected cells and cancer cells, and are crucial players of the human immune defense system. Although the relevant molecular machineries involved in NK cell activation and NK-target cell interactions are largely known, how their collective signaling modulates the dynamic behaviors of NK cells, e.g., motility and cytotoxicity, and the rate-limiting kinetics involved are still in need of comprehensive investigations. In traditional bulk killing assays, heterogeneity and kinetic details of individual NK-target cell interactions are masked, seriously limiting analysis of the underlying dynamic mechanisms. Here we present detailed protocols of a number of live-cell imaging assays using fluorescent protein reporters and/or a live-cell dye that enable the acquisition of quantitative kinetic data at the single cell level for elucidating the mechanism underlying the interaction dynamics of primary human NK cells and epithelial cancer cells. Moreover, we discuss how the imaging data can be analyzed either alone or in combination to quantify and determine the key dynamic steps/intermediates involved in specific NK cell activity, e.g., NK cell cytotoxic modes and their associated kinetics, and NK cell motility toward different cancer targets. These live-cell imaging assays can be easily adapted to analyze the rate-limiting kinetics and heterogeneity of other cell-cell interaction dynamics, e.g., in T cell function.

TRENDS IN VACCINE DEVELOPMENT: A REVIEW ARTICLE

A vaccine is a substance that boosts the immune system's defenses against disease. Most vaccines are given by needle injection, although some can also be taken by mouth or sprayed into the nose. The majority of vaccines have been in use for many years, and every year millions of individuals receive them safely. Every vaccine, like other pharmaceuticals, must undergo thorough and stringent testing to guarantee its safety before being included in a nation's vaccination program. The best antigen to employ to elicit an immune response must first be determined for each vaccination that is currently being developed. There are no human tests conducted during this preclinical stage. To gauge the safety and disease-prevention potential of an investigational vaccination, animals are used for the initial testing.

The Role of Nucleases Cleaving TLR3, TLR7/8 and TLR9 Ligands, Dicer RNase and miRNA/piRNA Proteins in Functional Adaptation to the Immune Escape and Xenophagy of Prostate Cancer Tissue.

The prototypic sensors for the induction of innate and adaptive immune responses are the Toll-like receptors (TLRs). Unusually high expression of TLRs in prostate carcinoma (PC), associated with less differentiated, more aggressive and more propagating forms of PC, changed the previous paradigm about the role of TLRs strictly in immune defense system. Our data reveal an entirely novel role of nucleic acids-sensing Toll-like receptors (NA-TLRs) in functional adaptation of malignant cells for supply and digestion of surrounding metabolic substrates from dead cells as specific mechanism of cancer cells survival, by corresponding ligands accelerated degradation and purine/pyrimidine salvage pathway. The spectrophotometric measurement protocols used for the determination of the activity of RNases and DNase II have been optimized in our laboratory as well as the enzyme-linked immunosorbent method for the determination of NF-κB p65 in prostate tissue samples. The protocols used to determine Dicer RNase, AGO2, TARBP2 and PIWIL4 were based on enzyme-linked immunosorbent assay. The amount of pre-existing acid-soluble oligonucleotides was measured and expressed as coefficient of absorbance. The activities of acid DNase II and RNase T2, and the activities of nucleases cleaving TLR3, TLR7/8 and TLR9 ligands (Poly I:C, poly U and unmethylated CpG), increased several times in PC, compared to the corresponding tumor adjacent and control tissue, exerting very high sensitivity and specificity of above 90%. Consequently higher levels of hypoxanthine and NF-κB p65 were reported in PC, whereas the opposite results were observed for miRNA biogenesis enzyme (Dicer RNase), miRNA processing protein (TARB2), miRNA-induced silencing complex protein (Argonaute-AGO) and PIWI-interacting RNAs silence transposon. Considering the crucial role of purine and pyrimidine nucleotides as energy carriers, subunits of nucleic acids and nucleotide cofactors, future explorations will be aimed to design novel anti-cancer immune strategies based on a specific acid endolysosomal nuclease inhibition.

A novel AIRE-based fluorescent ratiometric probe with endoplasmic reticulum-targeting ability for detection of hypochlorite and bioimaging

Hypochlorite (ClO−) plays an important role in the human immune defense system, but high concentrations of ClO− in the endoplasmic reticulum (ER) damage cellular proteins, causing ER stress, cell death, and various diseases. Herein, we developed a simple hydrazone probe (1) featuring aggregation-induced ratiometric emission, which would quickly (within 20 s) and sensitively (detection limit of 15.4 μM) respond to ClO− in an almost pure aqueous solution via a fluorescent ratiometric output. Furthermore, the probe was employed to track the level of ClO− in the ER of HeLa cells and zebrafish.

Circadian metabolism regulates the macrophage inflammatory response

Abstract Macrophages are an integral part of the innate immune system and coordinate host defense to microbial infections, as well as shaping the remodeling response after tissue injury. Metabolism is now appreciated to be a powerful and pervasive regulator of the identity and function of macrophages. Upon exposure to microbial ligands, macrophage inflammatory activation and the associated induction of phagocytosis, inflammatory responses, and other host defense activities are supported by dynamic changes to cellular metabolism. Of note, metabolic activity is robustly regulated in a circadian fashion, with many metabolic processes displaying peak activity in one phase of the circadian cycle and trough activity in an antiphase manner. Here, we review recent findings suggesting that circadian metabolism influences macrophage activities and particularly the inflammatory response. First, we summarize macrophage activities known to display time-of-day–dependent variation and their mechanistic basis. Second, we review metabolic processes that have been shown to be rhythmically regulated in macrophages and discuss how such circadian metabolism affects or is likely to affect macrophage activities. Third, we discuss the concept of entrainment of the macrophage clock, and consider how loss of rhythmic regulation of macrophage activities may contribute to pathophysiological conditions like shift work, obesity, and aging. Finally, we propose that circadian metabolism can be used to understand the rationale and mechanistic basis of dynamic regulation of inflammatory responses during infection.

Comprehensive assessment on the applications of oncolytic viruses for cancer immunotherapy.

The worldwide burden of cancers is increasing at a very high rate, including the aggressive and resistant forms of cancers. Certain levels of breakthrough have been achieved with the conventional treatment methods being used to treat different forms of cancers, but with some limitations. These limitations include hazardous side effects, destruction of non-tumor healthy cells that are rapidly dividing and developing, tumor resistance to anti-cancer drugs, damage to tissues and organs, and so on. However, oncolytic viruses have emerged as a worthwhile immunotherapeutic option for the treatment of different types of cancers. In this treatment approach, oncolytic viruses are being modeled to target cancer cells with optimum cytotoxicity and spare normal cells with optimal safety, without the oncolytic viruses themselves being killed by the host immune defense system. Oncolytic viral infection of the cancer cells are also being genetically manipulated (either by removal or addition of certain genes into the oncolytic virus genome) to make the tumor more visible and available for attack by the host immune cells. Hence, different variants of these viruses are being developed to optimize their antitumor effects. In this review, we examined how grave the burden of cancer is on a global level, particularly in sub-Saharan Africa, major conventional therapeutic approaches to the treatment of cancer and their individual drawbacks. We discussed the mechanisms of action employed by these oncolytic viruses and different viruses that have found their relevance in the fight against various forms of cancers. Some pre-clinical and clinical trials that involve oncolytic viruses in cancer management were reported. This review also examined the toxicity and safety concerns surrounding the adoption of oncolytic viro-immunotherapy for the treatment of cancers and the likely future directions for researchers and general audience who wants updated information.

Tumor Colonization and Therapy by Escherichia coli Nissle 1917 Strain in Syngeneic Tumor-Bearing Mice Is Strongly Affected by the Gut Microbiome.

In the past, different bacterial species have been tested for cancer therapy in preclinical and clinical studies. The success of bacterial cancer therapy is mainly dependent on the ability of the utilized bacteria to overcome the host immune defense system to colonize the tumors and to initiate tumor-specific immunity. In recent years, several groups have demonstrated that the gut microbiome plays an important role of modulation of the host immune response and has an impact on therapeutic responses in murine models and in cohorts of human cancer patients. Here we analyzed the impact of the gut microbiome on tumor colonization and tumor therapy by the Escherichia coli Nissle 1917 (EcN) strain. This EcN strain is a promising cancer therapy candidate with probiotic properties. In our study, we observed significantly better tumor colonization by EcN after antibiotic-induced temporal depletion of the gut microbiome and after two intranasal applications of the EcN derivate (EcN/pMUT-gfp Knr) in 4T1 tumor-bearing syngeneic BALB/c mice. In addition, we demonstrated significant reduction in tumor growth and extended survival of the EcN-treated mice in contrast to phosphate-buffered saline (PBS)-treated tumor-bearing control animals. Multispectral imaging of immune cells revealed that depletion of the gut microbiome led to significantly lower infiltration of cytotoxic and helper T cells (CD4 and CD8 cells) in PBS tumors of mice pretreated with antibiotics in comparison with antibiotic untreated PBS-or EcN treated mice. These findings may help in the future advancement of cancer treatment strategies using E. coli Nissle 1917.

Proteome-wide analysis of hydrogen peroxide-induced protein carbonylation in Arabidopsis thaliana.

Protein carbonylation is a non-enzymatic and irreversible post-translational modification that occurs naturally in living organisms under the direct or indirect effect of reactive oxygen species (ROS). In animals, signaling pathways involving numerous carbonylated proteins have been identified, highlighting the dual role of these molecules in ROS signal transduction. In plants, studies on phytohormone signaling (auxin, methyl jasmonate, abscisic acid) have shown that reactive carbonyl species (RCS: acrolein, malondialdehyde, 4-hydroxynonenal, etc.), derived from the action of ROS on lipids, play important roles in secondary root formation and stomatal closure. However, the carbonylated proteins involved in these signaling pathways remain to be identified. In this study, we analyzed proteins responsive to carbonylation by exogenous hydrogen peroxide (H2O2) by profiling the carbonyl proteome extracted from Arabidopsis thaliana leaves after H2O2 treatment. Carbonylated proteins were enriched at the peptide level and analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). We identified 35 and 39 uniquely carbonylated proteins in the untreated and the H2O2-treated plant samples, respectively. In comparison to the control treatment, gene ontology enrichment analysis revealed that most of the carbonylated proteins identified in the H2O2-treated plant samples are related to sulfate adenylyl transferases and amidophosphoribosyl transferases involved in the immune system response, defense response, and external stimulus-response. These results indicated that exogenous H2O2 caused a change in the pattern of protein carbonylation in A. thaliana leaves. Protein carbonylation may thus influence the plant transcriptome and metabolism in response to H2O2 and ROS-triggering external stimuli.

The Intestinal Immune Defense System in Insects

Over a long period of evolution, insects have developed unique intestinal defenses against invasion by foreign microorganisms, including physical defenses and immune responses. The physical defenses of the insect gut consist mainly of the peritrophic matrix (PM) and mucus layer, which are the first barriers to pathogens. Gut microbes also prevent the colonization of pathogens. Importantly, the immune-deficiency (Imd) pathways produce antimicrobial peptides to eliminate pathogens; mechanisms related to reactive oxygen species are another important pathway for insect intestinal immunity. The janus kinase/STAT signaling pathway is involved in intestinal immunity by producing bactericidal substances and regulating tissue repair. Melanization can produce many bactericidal active substances into the intestine; meanwhile, there are multiple responses in the intestine to fight against viral and parasitic infections. Furthermore, intestinal stem cells (ISCs) are also indispensable in intestinal immunity. Only the coordinated combination of the intestinal immune defense system and intestinal tissue renewal can effectively defend against pathogenic microorganisms.

Spaetzle responds to the process of Neoseiulus barkeri resistance to Beauveria bassiana infection

The application of Beauveria bassiana is proved to be a feasible biological control measure against pest insects and mites (e.g. Liu et al. 2018; Al Khoury et al. 2020). But the complex and variable ecological environment can affect the efficiency of B. bassiana. Due to the powerful search and spread ability of predatory mites, they were proposed to carry and spread pathogenic microbial spores to places that are difficult to be covered by conventional spray methods (Chen et al. 2020; Hao et al. 2021). This biocontrol strategy of combining fungi with predator mites is predicted to play a synergistic role in pest control. Therefore, the tolerance of predator mites to B. bassiana and the underlying mechanism have been the subject of extensive research and remained to be explored further. The infection of insects by B. bassiana can induce insect innate immune response. Spaetzle protein (Spz), as an important ligand of insect Toll pathway, has been demonstrated to play an important role in insect innate immune defense system. 

Transcriptome Profiling in the Hippocampi of Mice with Experimental Autoimmune Encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), approximates the key histopathological, clinical, and immunological features of MS. Hippocampal dysfunction in MS and EAE causes varying degrees of cognitive and emotional impairments and synaptic abnormalities. However, the molecular alterations underlying hippocampal dysfunctions in MS and EAE are still under investigation. The purpose of this study was to identify differentially expressed genes (DEGs) in the hippocampus of mice with EAE in order to ascertain potential genes associated with hippocampal dysfunction. Gene expression in the hippocampus was analyzed by RNA-sequencing and validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Gene expression analysis revealed 1202 DEGs; 1023 were upregulated and 179 were downregulated in the hippocampus of mice with EAE (p-value < 0.05 and fold change >1.5). Gene ontology (GO) analysis showed that the upregulated genes in the hippocampi of mice with EAE were associated with immune system processes, defense responses, immune responses, and regulation of immune responses, whereas the downregulated genes were related to learning or memory, behavior, and nervous system processes in the GO biological process. The expressions of hub genes from the search tool for the retrieval of interacting genes/proteins (STRING) analysis were validated by RT-qPCR. Additionally, gene set enrichment analysis showed that the upregulated genes in the hippocampus were associated with inflammatory responses: interferon-γ responses, allograft rejection, interferon-α responses, IL6_JAK_STAT3 signaling, inflammatory responses, complement, IL2_STAT5 signaling, TNF-α signaling via NF-κB, and apoptosis, whereas the downregulated genes were related to synaptic plasticity, dendritic development, and development of dendritic spine. This study characterized the transcriptome pattern in the hippocampi of mice with EAE and signaling pathways underpinning hippocampal dysfunction. However, further investigation is needed to determine the applicability of these findings from this rodent model to patients with MS. Collectively, these results indicate directions for further research to understand the mechanisms behind hippocampal dysfunction in EAE.

Human Papillomavirus E1 Protein Regulates Gene Expression in Cells Involved in Immune Response.

Human papillomavirus belongs to papovaviridae family papillomavirus A, a spherical deoxyribonucleic acid (DNA) virus, which can cause the proliferation of squamous epithelial cells of human skin or mucous membranes. With the rapid increase in the incidence of condyloma acuminatum among STDs and the increase in diseases caused by HPV infection, HPV infection has seriously endangered human health. In this paper, the in vitro detection of HPV E1 protein was realized using AgNCs-dsDNA. And through the test of this detection method, we calculated that the detection limit of this method is 0.886nM. Compared with other methods for detecting E1 protein in vitro, this method has high sensitivity and simple operation. In addition, the detection method also has good anti-interference and selectivity, and can realize the detection of E1 in serum samples. The transfection efficiency of BLV-miR-B4-3p mimics at different time points was determined by quantitative real-time PCR (qPCR); the transcriptome sequencing of lymphocytes transfected with different concentrations of BLV-miR-B4-3p mimics was performed, and differential gene clustering was performed on the sequencing results. And the BLV-miR-B4-3p target gene prediction and transcriptome analysis results were verified by qPCR. The effects of BLV-miR-B4-3p on the transcriptional levels of immune-related cytokines in human lymphocytes were analyzed. Transcriptome sequencing analysis showed that after BLV-miR-B4-3p entered lymphocytes, a total of 556 differentially expressed genes were obtained. GO enrichment and KEGG analysis results showed that BLV-miR-B4-3p could independently activate influenza. The signaling pathway ultimately affects the body's immune system process, stress response, defense response, immune response, and other biological processes. After BLV-miR-B4-3p enters lymphocytes, it will lead to abnormal lymphocyte immune function, including the mRNA expression of TNF-α in Th1 cytokines which was significantly increased (P < 0.05), and the expression of IL-10 in Th2 cytokines was significantly increased (P < 0.05). The mRNA expression was significantly decreased (P < 0.05), and the mRNA expression of IL-27 was significantly increased (P < 0.001), which did not affect the mRNA expression of lymphocyte proliferation and activation-related regulators. The tumor suppressor breast cancer 1 (BRCA1) and antimicrobial peptide CAMP were significantly increased, and decreased (P < 0.001), and the expression of pro-apoptotic factor Caspase9 showed a significant downward trend (P < 0.05).

Increased risk of COVID-19 mortality rate in IFITM3 rs6598045 G allele carriers infected by SARS-CoV-2 delta variant

BackgroundThe interferon-induced transmembrane-protein 3 (IFITM3) is a vital component of the immune system's defense against viral infection. Variants in the IFITM3 gene have been linked to changes in expression and the risk of severe Coronavirus disease 2019 (COVID-19). This study aimed to investigate whether IFITM3 rs6598045, quantitative polymerase chain reaction (qPCR) cycle threshold (Ct) values, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are associated with an increased mortality rate of COVID-19.MethodsThe genotyping of IFITM3 rs6598045 polymorphism was analyzed using the amplification refractory mutation system-polymerase chain reaction in 1342 recovered and 1149 deceased patients positive for SARS-CoV-2.ResultsIn this study, IFITM3 rs6598045 G allele as minor allele frequency was significantly more common in the deceased patients than in the recovered ones. Furthermore, the highest mortality rates were observed in Delta variant and lowest qPCR Ct values. COVID-19 mortality was associated with IFITM3 rs6598045 GG and AG in Delta variant and IFITM3 rs6598045 AG in Alpha variant. A statistically significant difference was observed in the qPCR Ct values between individuals with GG and AG genotypes and those with an AA genotype.ConclusionA possible correlation was observed between the mortality rate of COVID-19, the G allele of IFITM3 rs6598045, and SARS-CoV-2 variants. However, large-scale research is still required to validate our results.

Current Knowledge on Bee Innate Immunity Based on Genomics and Transcriptomics.

As important pollinators, bees play a critical role in maintaining the balance of the ecosystem and improving the yield and quality of crops. However, in recent years, the bee population has significantly declined due to various pathogens and environmental stressors including viruses, bacteria, parasites, and increased pesticide application. The above threats trigger or suppress the innate immunity of bees, their only immune defense system, which is essential to maintaining individual health and that of the colony. In addition, bees can be divided into solitary and eusocial bees based on their life traits, and eusocial bees possess special social immunities, such as grooming behavior, which cooperate with innate immunity to maintain the health of the colony. The omics approach gives us an opportunity to recognize the distinctive innate immunity of bees. In this regard, we summarize innate bee immunity from a genomic and transcriptomic perspective. The genetic characteristics of innate immunity were revealed by the multiple genomes of bees with different kinds of sociality, including honeybees, bumblebees, wasps, leaf-cutter bees, and so on. Further substantial transcriptomic data of different tissues from diverse bees directly present the activation or suppression of immune genes under the infestation of pathogens or toxicity of pesticides.

Combined use of lactoferrin and vitamin D as a preventive and therapeutic supplement for SARS-CoV-2 infection: Current evidence.

Lactoferrin is a multifunctional protein that exhibits anti-inflammatory, immune regulating and anti-infective properties. One of its receptor sites is located on severe acute respiratory syndrome coronavirus 2. The binding of lactoferrin with heparin sulfate proteoglycans may prevent the first contact between the virus and host cells, thus preventing subsequent infection. Given that lactoferrin may act as a natural mucosal barrier, an intranasal treatment together with its oral intake can be hypothesized to prevent the spread, infection and inflammation caused by coronavirus disease 2019 (COVID-19). Moreover, the literature reports that vitamin D plays an essential role in promoting immune response. With its anti-inflammatory and immunoregulatory properties, vitamin D is critical for activating the immune system's defenses, improving immune cell function. Different studies also demonstrate that lactoferrin is a potential activator of the vitamin D receptor. In this sense, the combined use of lactoferrin (through an association of oral intake and a nasal spray formulation) and vitamin D could represent a valuable therapy for COVID-19 treatment and prevention. However, further randomized clinical trials are needed before recommending/prescribing them.

Chronic effects of environmental concentrations of antifoulant diuron on two marine fish: Assessment of hormone levels, immunity, and antioxidant defense system

The presence and toxicity of waterborne diuron in aquatic environments pose a severe threat to non-target organisms. However, the chronic impact of diuron in marine fish has been poorly investigated. In this study, we report the chronic effects (30 and 60 days) of environmentally relevant concentrations of diuron (0.1, 1, and 10 μg L−1) on economically important marine fish, red seabream (Pagrus major), and black rockfish (Sebastes schlegelii) by evaluating several parameters, including hormone levels, immunity, hepatic function, and antioxidant defense. Significant decreases in 17β–estradiol and 11–ketotestosterone levels and gonadosomatic index were observed on day 60 in fish exposed to 10 μg L−1 diuron. Parameters of immunity, such as alternative complement activity, lysozyme activity, and total immunoglobulin levels, were significantly lowered by 60-day exposure to 10 μg L−1 diuron in both fish. Significant decreases in the hepatic enzyme activities of alanine transaminase and aspartate transaminase were observed with an induction of cortisol on day 60 in fish exposed to 10 μg L−1 diuron. Intracellular malondialdehyde and glutathione levels were significantly increased by 10 μg L−1 diuron at day 60 with an increase in the enzymatic activities of catalase and superoxide dismutase. Overall, black rockfish were more sensitive to diuron than red seabream. These results suggest that consistent exposure to environmentally relevant concentrations of diuron is detrimental to the reproduction, immunity, and health of marine fish.

Research progress of effect of neutrophil elastase and its inhibitors in sepsis

Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by infection. When an infection occurs, as the first line of defense of the body's immune system, neutrophils are first recruited to the site of infection to capture and kill pathogens by releasing neutrophil elastase (NE). However, a large amount of NE release will injury the surrounding normal tissues and induce organ dysfunction or failure. NE inhibitors can inhibit NE activity and reduce inflammatory response, which may be a promising drug for the treatment of sepsis. Currently, a variety of NE inhibitors have been developed and reported, but there is no systematic overview of their characteristics, and the role and underlying mechanisms of NE and related inhibitors in sepsis have not been thoroughly discussed. This article will make a review in this regard, in order to elucidate the effect of NE and its inhibitors in sepsis.

Galectin-1 from redlip mullet Liza haematocheilia: identification, immune responses, and functional characterization as pattern recognition receptors (PRRs) in host immune defense system

Galectins, a family of β-galactoside-binding lectins, have emerged as soluble mediators in infected cells and pattern recognition receptors (PRRs) responsible for evoking and regulating innate immunity. The present study aimed to evaluate the role of galectin-1 in the host immune response of redlip mullet (Liza haematocheilia). We established a cDNA database for redlip mullet, and the cDNA sequence of galectin-1 (LhGal-1) was characterized. In silico analysis was performed, and the spatial and temporal expression patterns in gills and blood in response to lipopolysaccharide polyinosinic:polycytidylic acid, and Lactococcus garvieae were estimated via quantitative real-time PCR. Functional assays were conducted using recombinant protein to investigate carbohydrate binding, bacterial binding, and bacterial agglutination activity. LhGal-1 was composed of 135 amino acids. Conserved motifs (H-NPR, -N- and -W-E-R) within the carbohydrate recognition domain were found in LhGal-1. The tissue distribution revealed that the healthy stomach expressed high levels of LhGal-1. The temporal monitoring of LhGal-1 mRNA expression in the gill and blood showed its significant upregulation in response to immune challenges with different stimulants. rLhGal-1 exhibited binding activity in response to carbohydrates and bacteria. Moreover, the agglutination of rLhGal-1 against Escherichia coli was observed. Collectively, our findings suggest that LhGal-1 may function as a PRR in redlip mullet. Furthermore, LhGal-1 can be considered a significant gene to play a protective role in redlip mullet immune system.

Epigenetics for crop adaptation to climate change

Epigenetics for crop adaptation to climate change

A preliminary report of exploration of the exosomal shuttle protein in marine invertebrate Chlamys farreri

Exosomes are extracellular vesicles secreted by diverse cell under normal or abnormal physiological conditions, which could carry a range of bioactive molecules and play significant roles in biological processes, such as intercellular communication and immune response. In the current study, a preliminary study was performed to investigate the exosomal shuttle protein in Chlamys farreri (designated as CfesPro) and to predict the potential function of exosomes in scallop innate immunity. The serum derived exosomes (designated as CfEVs) were obtained from lipopolysaccharide (LPS)-stimulated C. farreri and untreated ones. After confirmation and characterization by transmission electron microscopy (TEM), nano-HPLC-MS/MS spectrometry was performed on CfEVs using a label-free quantitative method. Totally 2481 exosomal shuttle proteins were identified in CfEVs proteomic data, which included many innate immune related proteins. GO and KOG functional annotation showed that CfesPro participated in cellular processes, metabolism reactions, signaling transductions, immune responses and so on. Moreover, 1421 proteins in CfesPro were enriched to 324 pathways by KEGG analysis, including several immune-related pathways, such as autophagy, apoptosis and lysosome pathway. Meanwhile, eight autophagy-related proteins were initially identified in CfesPro, indicating that CfEVs had a potential role with autophagy. All these findings showed that CfEVs were involved in C. farreri innate immune defenses. This research would enrich the protein database of marine exosomes and provide a basis for the exploration of immune defense systems in marine invertebrates.