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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Relation between neonatal malnutrition and gene expression: inflammasome function in infections caused by Candida
Thacianna Barreto Da Costa1,2, Natália Gomes De Morais3,4, Joana Maria Bezerra De Lira4
1Department of Tropical Medicine, Federal University of Pernambuco, Recife, Brazil. thaciannabc@gmail.com.
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.
Insights
Neonatal malnutrition impacts inflammasome complex signaling in rats, with nutritional replacement partially restoring defense mechanisms against opportunistic pathogens like Candida albicans.
Area of Science:
- Immunology
- Nutritional Science
- Cellular Biology
Background:
- Neonatal malnutrition can impair immune system development.
- The inflammasome complex plays a crucial role in innate immunity.
- Alveolar macrophages are key immune cells in the lungs.
Purpose of the Study:
- To investigate the long-term effects of neonatal malnutrition and subsequent nutritional rehabilitation on inflammasome complex signaling pathways.
- To analyze the expression of Toll-like receptors (TLR2, TLR4), NLRP3, and caspase-1, and the release of IL-1β and IL-18 in alveolar macrophages.
- To assess the immune response of these macrophages to Candida albicans infection in vitro.
Main Methods:
- Male Wistar rats were divided into nourished and malnourished groups based on maternal lactation diet (17% vs. 8% protein).
- After weaning, all rats received a normal protein diet.
- Alveolar macrophages were isolated via bronchoalveolar lavage fluid.
- Gene expression of TLR2, TLR4, NLRP3, and caspase-1 was quantified using real-time RT-PCR.
- Cytokine production (IL-1β, IL-18) was measured by ELISA.
Main Results:
- Malnourished rats exhibited reduced body weight persisting into adulthood.
- Malnutrition led to decreased expression of TLR4 and caspase-1.
- Expression of TLR2 and NLRP3, and release of IL-1β and IL-18, were not significantly different between nourished and malnourished groups.
- In vitro Candida albicans infection induced high expression of all studied targets in both groups.
Conclusions:
- Nutritional restriction during development, even with later supplementation, can alter immune defense patterns.
- Specific inflammasome signaling pathways may be preserved, mitigating extreme vulnerability to opportunistic infections.
- The study highlights the lasting impact of early-life nutrition on immune responses.

