Relation between neonatal malnutrition and gene expression: inflammasome function in infections caused by Candida Albicans

Eur J Nutr. 2017 Mar;56(2):693-704. doi: 10.1007/s00394-015-1113-9. Epub 2015 Dec 11.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Candida albicans; Macrophage; NOD-like receptors; Neonatal malnutrition; Programming; Toll-like receptors.

MeSH terms

  • Animals
  • Animals, Newborn
  • Bronchoalveolar Lavage Fluid / immunology
  • Bronchoalveolar Lavage Fluid / microbiology
  • Candida albicans / immunology
  • Candidiasis / immunology
  • Candidiasis / metabolism*
  • Candidiasis / microbiology
  • Candidiasis / pathology
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Cells, Cultured
  • Diet, Protein-Restricted / adverse effects*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Developmental*
  • Immunity, Innate
  • Inflammasomes / immunology
  • Inflammasomes / metabolism*
  • Lactation
  • Macrophage Activation / immunology
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / metabolism*
  • Macrophages, Alveolar / microbiology
  • Macrophages, Alveolar / pathology
  • Male
  • Maternal Nutritional Physiological Phenomena*
  • Opportunistic Infections / immunology
  • Opportunistic Infections / metabolism*
  • Opportunistic Infections / microbiology
  • Opportunistic Infections / pathology
  • Rats, Wistar
  • Thinness / etiology
  • Thinness / immunology
  • Thinness / microbiology
  • Thinness / pathology
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism

Substances

  • Inflammasomes
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Caspase 1