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Extracellular vesicles modulate host-microbe responses by altering TLR2 activity and phagocytosis.

ABSTRACT: Oral delivery of Gram positive bacteria, often derived from the genera Lactobacillus or Bifidobacterium, can modulate immune function. Although the exact mechanisms remain unclear, immunomodulatory effects may be elicited through the direct interaction of these bacteria with the intestinal epithelium or resident dendritic cell (DC) populations. We analyzed the immune activation properties of Lactobacilli and Bifidobacterium species and made the surprising observation that cellular responses in vitro were differentially influenced by the presence of serum, specifically the extracellular vesicle (EV) fraction. In contrast to the tested Lactobacilli species, tested Bifidobacterium species induce TLR2/6 activity which is inhibited by the presence of EVs. Using specific TLR ligands, EVs were found to enhance cellular TLR2/1 and TLR4 responses while TLR2/6 responses were suppressed. No effect could be observed on cellular TLR5 responses. We determined that EVs play a role in bacterial aggregation, suggesting that EVs interact with bacterial surfaces. EVs were found to slightly enhance DC phagocytosis of Bifidobacterium breve whereas phagocytosis of Lactobacillus rhamnosus was virtually absent upon serum EV depletion. DC uptake of a non-microbial substance (dextran) was not affected by the different serum fractions suggesting that EVs do not interfere with DC phagocytic capacity but rather modify the DC-microbe interaction. Depending on the microbe, combined effects of EVs on TLR activity and phagocytosis result in a differential proinflammatory DC cytokine release. Overall, these data suggest that EVs play a yet unrecognized role in host-microbe responses, not by interfering in recipient cellular responses but via attachment to, or scavenging of, microbe-associated molecular patterns. EVs can be found in any tissue or bodily fluid, therefore insights into EV-microbe interactions are important in understanding the mechanism of action of potential probiotics and gut immune homeostasis.

SUBMITTER: van Bergenhenegouwen J

PROVIDER: S-EPMC3930685 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Extracellular vesicles modulate host-microbe responses by altering TLR2 activity and phagocytosis.

van Bergenhenegouwen Jeroen J Kraneveld Aletta D AD Rutten Lieke L Kettelarij Nienke N Garssen Johan J Vos Arjan P AP

PloS one 20140220 2

Oral delivery of Gram positive bacteria, often derived from the genera Lactobacillus or Bifidobacterium, can modulate immune function. Although the exact mechanisms remain unclear, immunomodulatory effects may be elicited through the direct interaction of these bacteria with the intestinal epithelium or resident dendritic cell (DC) populations. We analyzed the immune activation properties of Lactobacilli and Bifidobacterium species and made the surprising observation that cellular responses in v ...[more]

PMID: 24586537

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Project description:Trypanosoma cruzi is the protozoan that causes Chagas disease (CD), an endemic parasitosis in Latin America distributed around the globe. If CD is not treated in acute phase, the parasite remains silent for years in the host's tissues in a chronic form, which may progress to cardiac, digestive or neurological manifestations. Recently, studies indicated that the gastrointestinal tract represents an important reservoir for T. cruzi in the chronic phase. During interaction T. cruzi and host cells release extracellular vesicles (EVs) that modulates the immune system and infection, but the dynamics of secretion of host and parasite molecules through these EVs is not understood. Now, we used two cell lines: mouse myoblast cell line C2C12, and human intestinal epithelial cell line Caco-2to simulate the environments found by the parasite in the host. We isolated large EVs (LEVs) from the interaction of T. cruzi CL Brener and Dm28c/C2C12 and Caco-2 cells upon 2 and 24 h of infection. Our data showed that at two hours there is a strong cellular response mediated by EVs, both in the number, variety and enrichment/targeting of proteins found in LEVs for diverse functions. Qualitative and quantitative analysis showed that proteins exported in LEVs of C2C12 and Caco-2 have different patterns. We found a predominance of host proteins at early infection. The parasite-host cell interaction induces a switch in the functionality of proteins carried by LEVs and a heterogeneous response depending on the tissues analyzed. Protein-protein interaction analysis showed that cytoplasmic and mitochondrial homologues of the same parasite protein, tryparedoxin peroxidase, were differentially packaged in LEVs, also impacting the interacting molecule of this protein in the host. These data provide new evidence that the interaction with T. cruzi leads to a rapid tissue response through the release of LEVs, reflecting the enrichment of some proteins that could modulate the infection environment.

Project description:Bifidobacteria are important gut commensals of mammals, including humans, of any age. However, the molecular mechanisms by which these microorganisms establish themselves in the mammalian gut and persist in this environment are largely unknown. Here, we analyzed the genetic diversity of the predicted arsenal of sortase-dependent pili of known and sequenced members of the Bifidobacterium genus and constructed a bifidobacterial sortase-dependent fimbriome database. Our analyses revealed considerable genetic variability of the sortase-dependent fimbriome among bifidobacterial (sub)species, which appears to have been due to horizontal gene transfer events and for which we were able to perform evolutionary mapping. Functional assessment by transcriptome analysis and binding assays involving different substrates demonstrates how bifidobacterial pili are pivotal in promoting various abilities for adhesion to glycans and extracellular matrix proteins, thereby supporting the ecological success of bifidobacteria in the mammalian gut.IMPORTANCE Adhesion of bifidobacterial cells to the mucosa of the large intestine is considered a hallmark for the persistence and colonization of these bacteria in the human gut. In this context, we analyzed the genetic diversity of the predicted arsenal of sortase-dependent pili of known and sequenced members of the Bifidobacterium genus, and constructed a bifidobacterial sortase-dependent fimbriome database. Our analyses revealed considerable genetic variability of the sortase-dependent fimbriome among bifidobacterial (sub)species, which appears to have been due to horizontal gene transfer events. In addition, functional assessment by transcriptome analysis and binding assays involving different substrates demonstrates how bifidobacterial pili are crucial in promoting various abilities for adhesion to glycans and extracellular matrix proteins, thereby supporting the ecological success of bifidobacteria in the mammalian gut. This study represents a complete genomic study regarding the presence of fimbriae in the genus Bifidobacterium.

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Extracellular vesicles modulate host-microbe responses by altering TLR2 activity and phagocytosis.

Publications

Extracellular vesicles modulate host-microbe responses by altering TLR2 activity and phagocytosis.

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