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Suppression of virus-induced CCL2, CXCL10 and IL-6: biomarkers of Lactobacillus-mediated protection at the respiratory tract

ABSTRACT: In this manuscript, we present a more extensive analysis of inflammatory suppression mediated by L. plantarum at the respiratory tract. Via full genome microarray of whole lung tissue, we have generated an extensive list of soluble proinflammatory mediators that are expressed in response to PVM infection and we identify those mediators that are suppressed and also those that are not suppressed in response to L. plantarum priming. We focused further study on three specific virus-induced soluble mediators that are differentially expressed and that serve as specific biomarkers for Lactobacillus-mediated survival in response to acute respiratory virus infection. Among several novel directions, we use these biomarker cytokines to explore Lactobacillus-mediated actions at the respiratory tract that are unique and distinct from those taking place at gastrointestinal mucosa.

ORGANISM(S): Mus musculus

PROVIDER: GSE66721 | GEO | 2015/11/02

SECONDARY ACCESSION(S): PRJNA277807

REPOSITORIES: GEO

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Project description:Background: Lactobacillus plantarum is found in a variety of fermented foods and as such, consumed for centuries. Some strains are natural inhabitants of the human gastro-intestinal tract and like other Lactobacillus species, L. plantarum has been extensively studied for its immunomodulatory properties and its putative health-promoting effects (probiotic). Being the first line of host defense intestinal epithelial cells (IEC) are key players in the recognition and initiation of responses to gut microorganisms. Results: Using high-density oligonucleotide microarrays we examined the gene expression profiles of differentiated Caco-2 cells exposed to various doses of L. plantarum. In addition, the effects were correlated to monolayer permeability studies and measurement of lactic acid production. A transcriptional dose-dependent IEC response to L. plantarum was found. Incubation of Caco-2 with a low bacterial dose induced a specific response, not due to cytotoxicity or production of lactic acid, including modulation of cell cycle and cell signaling functions. Exposure of Caco-2 cells to larger amounts of bacteria, accompanied by the production of lactic acid and glucose depletion, provoked increased permeability and supposed non-specific defense responses. Conclusions: These results suggest that IEC are able to sense and react to the presence of gut bacteria. This study provides the first description of global transcriptional response of human IEC to a commensal lactic acid bacterium, and it shows the importance of choosing physiological bacterial doses to prevent the observation of non-specific host reactions. Caco-2 cells were exposed for 10h to Lactobacillus. Fourteen samples are analyzed: 4 control Caco-2, 4 Caco-2 exposed to a low dose (10) of Lactobacillus, 4 Caco-2 exposed to a medium dose (100) of Lactobacillus, 2 Caco-2 exposed to a high dose (1000) of Lactobacillus. All 14 RNA samples are labeled with Cy5 and hybridized to a common reference (undifferentiated Caco-2, untreated) RNA labeled with Cy3

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Suppression of virus-induced CCL2, CXCL10 and IL-6: biomarkers of Lactobacillus-mediated protection at the respiratory tract

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