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Microbes Malnutrition Microglia

ABSTRACT: This study examines the role of early exposure to gut microbes and poor diet on microglial function in mice. Groups = control (CON), malnourished (MAL), and malnourished + microbial exposure (E/MALBG). CD11b+ cells (microglial enrichment) were isolated from whole mouse brains (Adult Brain Disruption Kit, Miltenyi Biotec). After sample quality control (Agilent 2100 Bioanalyzer), qualifying samples were sent for RNA-Seq (Illumina NextSeq 500 with Paired End 42bp × 42bp reads; demultiplexed: Illumina's bcl2fastq2). Following alignment against mouse reference genes (STAR aligner), DEG analyses was conducted using the DESeq2 pipeline.

ORGANISM(S): Mus musculus

PROVIDER: GSE138182 | GEO | 2021/05/31

REPOSITORIES: GEO

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Project description:The thymus is one of the most affected organs during malnutrition, exhibiting atrophy and thymocyte depletion, characteristics that are also observed in several infectious diseases. The detrimental effects of malnutrition on immune responses to pathogens have long been recognized and it is considered a main risk factor for various infectious diseases, including visceral leishmaniasis (VL). However, the thymus has been barely studied during malnutrition and Leishmania infantum infection association. Protein malnutrition modifies intrathymic communication in L. infantum infected BALB/c mice by altering the abundance of proteins secreted to the thymic interstitial fluid (IF). We identified and compared protein abundance in the thymic IF samples from BALB/c mice that were fed with control protein (14%, CP) or low protein (4%, LP) isocaloric diets, followed by infection with L. infantum. By means of a quantitative proteomics approach using iTRAQ we identified 280 proteins of which 81% were reported as secreted by exosomes and 42% were previously described as secreted by thymic epithelial cells. LP-infected (LPi) animals showed a significant decrease in exosomal proteins, suggesting that exosomal carrier system is dysregulated in malnourished animals. LPi mice also exhibited an increase in the relative abundance of proteins involved in lipid metabolism and tricarboxylic acid cycle, suggestive of a non-proliferative microenvironment. Accordingly, flow cytometry analysis revealed that protein malnutrition decreases the proliferation of single positive and double positive T cells. Proteins engaged in glycolysis, protein ubiquitination and mRNA processing were significantly decreased. In addition, a significant decrease in the abundance of galectin-1 and increase of plasminogen were observed in malnourished animals. Together, the reduced cortical area, decreased proliferation, increased abundance of lipid- and tricarboxylic acid cycle-related proteins, and altered abundance of galectin-1 and plasminogen indicate a dysfunctional thymic microenvironment, where T cell migration, proliferation and maturation are compromised, contributing for the thymic atrophy observed in malnourished animals. All these alterations affect the control of the local and systemic infection, resulting in an impaired response to L. infantum infection.

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Microbes Malnutrition Microglia

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