Proteomic analysis and immune properties of exosomes released by macrophages infected with Mycobacterium avium

Wang, Jianjun; Chen, Cai; Xie, Ping-fang; Pan, Yi; Tan, Yun‐Hong; Tang, Lijun

doi:10.1016/j.micinf.2013.12.001

Cited by 54 publications

(40 citation statements)

References 49 publications

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“…We determined that Mycobacterium avium ‐infected macrophages release vesicles that can stimulate a pro‐inflammatory response in non‐infected or ‘bystander’ macrophages . Similar results were reported by Wang and colleagues . Anand and colleagues observed increased exosome production in macrophages infected with M. avium and M. smegmatis compared to uninfected cells, as well as increased levels of the host protein HSP70, a protein they found could activate macrophages in vitro .…”

Section: Exosomes and Other Extracellular Vesicles In Infectious Diseasesupporting

confidence: 82%

Exosomes and other extracellular vesicles in host–pathogen interactions

et al. 2014

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An effective immune response requires the engagement of host receptors by pathogen-derived molecules and the stimulation of an appropriate cellular response. Therefore, a crucial factor in our ability to control an infection is the accessibility of our immune cells to the foreign material. Exosomes-which are extracellular vesicles that function in intercellular communication-may play a key role in the dissemination of pathogen-as well as host-derived molecules during infection. In this review, we highlight the composition and function of exosomes and other extracellular vesicles produced during viral, parasitic, fungal and bacterial infections and describe how these vesicles could function to either promote or inhibit host immunity.

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Section: Exosomes and Other Extracellular Vesicles In Infectious Diseasesupporting

confidence: 82%

Exosomes and other extracellular vesicles in host–pathogen interactions

et al. 2014

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“…Exosomes may also act as novel biomarkers in several diseases such as acute myeloid leukemia (AML), ovarian cancer, asthma and sarcoidosis [20, 24, 36]. The miRNA profile and some aspects of exosomal content has recently been examined in TB patients [18, 37, 52, 53]. In these studies, the levels of serum free miRNAs [54], macrophage cell miRNAs [55] and exosomal protein content [39] were evaluated.…”

Section: Discussionmentioning

confidence: 99%

Bovis Bacillus Calmette–Guerin (BCG) infection induces exosomal miRNA release by human macrophages

et al. 2017

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BackgroundTuberculosis (TB) remains a significant global health concern and its diagnosis is challenging due to the limitations in the specificity and sensitivity of the current diagnostic tests. Exosomes are bioactive 30–100 nm vesicles produced by most cell types and are found in almost all human body fluids. Exosomal microRNAs (miRNAs) can transfer biological information between cells and tissues and may act as potential biomarkers in many diseases. In this pilot study, we assessed the miRNA profile of exosomes released from human monocyte-derived macrophages upon infection with Mycobacterium bovis Bacillus Calmette–Guerin (BCG).MethodsHuman monocytes were obtained from the peripheral blood of three healthy subjects and driven to a monocyte-derived macrophage (MDM) phenotype using standard protocols. MDMs were infected with BCG or left uninfected as control. 72 h post-infection, exosomes were collected from the cell culture medium, RNA was isolated and RNA-seq performed. The raw reads were filtered to eliminate adaptor and primer sequences and the sequences were run against the mature human miRNA sequences available in miRBase. MicroRNAs were identified using an E value <0.01. miRNA network analysis was performed using the DIANA miRNA tool, miRDB and functional KEGG pathway analysis.ResultsInfection of MDMs with BCG leads to the release of several exosomal miRNAs. These included miR-1224, -1293, -425, -4467, -4732, -484, -5094, -6848-6849, -4488 and -96 all of which were predicted to target metabolism and energy production-related pathways.ConclusionsThis study provides evidence for the release of specific exosomal miRNAs from BCG-infected MDMs. These exosomal miRNAs reflect host-pathogen interaction and subversion of host metabolic processes following infection.

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“…albumin and immunoglobulins) while concentrating the bacterial products of interest. Recent studies have shown that proteins from other mycobacterial species, such as M. avium [21], as well as other intracellular pathogens, such as Helicobacter pylori [22] can be readily detected in exosomes. In the current study, we sought to confirm and build upon our previous discovery studies in which Mtb peptides for 33 unique Mtb proteins were detected in human serum or patients with active and/or latent TB [11].…”

Section: Discussionmentioning

confidence: 99%

Second generation multiple reaction monitoring assays for enhanced detection of ultra-low abundance Mycobacterium tuberculosis peptides in human serum

et al. 2017

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Background Mycobacterium tuberculosis (Mtb) is the causative agent of Tuberculosis (TB), the number one cause of death due to an infectious disease. TB diagnosis is performed by microscopy, culture or PCR amplification of bacterial DNA, all of which require patient sputum or the biopsy of infected tissue. Detection of mycobacterial products in serum, as biomarkers of diagnosis or disease status would provide an improvement over current methods. Due to the low-abundance of mycobacterial products in serum, we have explored exosome enrichment to improve sensitivity. Mtb resides intracellularly where its secreted proteins have been shown to be packaged into host exosomes and released into the bloodstream. Exosomes can be readily purified assuring an enrichment of mycobacterial analytes from the complex mix of host serum proteins.MethodsMultiple reaction monitoring assays were optimized for the enhanced detection of 41 Mtb peptides in exosomes purified from the serum of individuals with TB. Exosomes isolated from the serum of healthy individuals was used to create and validate a unique data analysis algorithm and identify filters to reduce the rate of false positives, attributed to host m/z interference. The final optimized method was tested in 40 exosome samples from TB positive patients.ResultsOur enhanced methods provide limit of detection and quantification averaging in the low femtomolar range for detection of mycobacterial products in serum. At least one mycobacterial peptide was identified in 92.5% of the TB positive patients. Four peptides from the Mtb proteins, Cfp2, Mpt32, Mpt64 and BfrB, show normalized total peak areas significantly higher in individuals with active TB as compared to healthy controls; three of the peptides from these proteins have not previously been associated with serum exosomes from individuals with active TB disease. Some of the detected peptides were significantly associated with specific geographical locations, highlighting potential markers that can be linked to the Mtb strains circulating within each given region.ConclusionsAn enhanced MRM method to detect ultra-low abundance Mtb peptides in human serum exosomes is demonstrated, highlighting the potential of this methodology for TB diagnostic biomarker development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-017-9156-y) contains supplementary material, which is available to authorized users.

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Proteomic analysis and immune properties of exosomes released by macrophages infected with Mycobacterium avium

Cited by 54 publications

References 49 publications

Exosomes and other extracellular vesicles in host–pathogen interactions

Exosomes and other extracellular vesicles in host–pathogen interactions

Bovis Bacillus Calmette–Guerin (BCG) infection induces exosomal miRNA release by human macrophages

Second generation multiple reaction monitoring assays for enhanced detection of ultra-low abundance Mycobacterium tuberculosis peptides in human serum

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