PXD010414

PXD010414 is an original dataset announced via ProteomeXchange.

Title	thymus mouse LC-MSMS - Thymic Microenvironment Is Modified by Malnutrition and Leishmania infantum Infection
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.
HostingRepository	PRIDE
AnnounceDate	2021-03-04
AnnouncementXML	Submission_2021-03-04_14:56:02.688.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Monica Losada
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iTRAQ4plex-116 reporter+balance reagent acylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-13 02:21:22	ID requested
⏵ 1	2021-03-04 14:56:03	announced

Losada-Barrag, á, n M, Uma, ñ, a-P, é, rez A, Dur, ã, es J, Cuervo-Escobar S, Rodr, í, guez-Vega A, Ribeiro-Gomes FL, Berbert LR, Morgado F, Porrozzi R, Mendes-da-Cruz DA, Aquino P, Carvalho PC, Savino W, S, á, nchez-G, ó, mez M, Padr, ó, n G, Cuervo P, Infection. Front Cell Infect Microbiol, 9():252(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: Thymus, mouse, fluid, malnutrition, LC-MSMS

Patricia Cuervo Escobar
contact affiliation	Laboratório de Pesquisa em Leishmanioses, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brasil
contact email	patricia.cuervo@fiocruz.br
lab head
Monica Losada
contact affiliation	Dr
contact email	moni.losada@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010414
     1. Label: PRIDE project
     2. Name: thymus mouse LC-MSMS - Thymic Microenvironment Is Modified by Malnutrition and Leishmania infantum Infection