Relation between neonatal malnutrition and gene expression: inflammasome function in infections caused by Candida Albicans
To investigate the effects of neonatal malnutrition followed by nutritional replacement on the signaling mechanisms developed by the inflammasome complex by analyzing the expression of the targeted TLR2, TLR4, NLRP3, caspase-1 and release of IL-1β and IL-18 by alveolar macrophages infected in vitro with Candida albicans.
Male Wistar rats (n = 24), 90–120 days, were suckled by mothers whose diet during lactation contained 17 % protein in the nourish group and 8 % protein in the malnourished group. After weaning, both groups were fed a normal protein diet. Macrophages were obtained after tracheostomy, through the collection of bronchoalveolar lavage fluid. The quantification of the expression levels of targets (TLR2, TLR4, NLRP3 and caspase-1) was performed by real-time RT-PCR. Production of cytokines was performed by ELISA.
The malnourished animals during lactation showed reduced body weight from the fifth day of life, remaining until adulthood. Further, the model applied malnutrition induced a lower expression of TLR4 and caspase-1. The quantification of the TLR2 and NLRP3, as well as the release of IL-1β and IL-18, was not different between groups of animals nourished and malnourished. The system challenged with Candida albicans showed high expression levels of all targets in the study.
The tests demonstrate nutritional restriction during critical periods of development, although nutritional supplementation may compromise defense patterns in adulthood in a timely manner, preserving distinct signaling mechanism, so that the individual does not become widely vulnerable to infections by opportunistic pathogens.
KeywordsNeonatal malnutrition Programming Macrophage Candida albicans Toll-like receptors NOD-like receptors
The authors wish to thank the Keizo Asami Immunopathology Laboratory of the Federal University of Pernambuco, Recife, Brazil, and Department of Immunology, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation, Campus UFPE, Recife, Brazil, for the structure and equipment provided for the development of this research.
The study was supported by National Counsel of Technological and Scientific Development (CNPq), Brazil, and partially funded by Dean of Research and Graduate Studies, Federal University of Pernambuco (PROPESQ/UFPE), Brazil.
Compliance with ethical standards
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
This study was approved by Ethics Committee on Animal Experimentation of the Center for Biological Sciences, Federal University of Pernambuco (CEEA-UFPE) (Pernambuco, Brazil, Protocol 23076.053096/2011-91 ). The manuscript does not contain clinical studies or patient data.
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