title: TLR and NLRP3 inflammasome expression deregulation in macrophages of adult rats subjected to neonatal malnutrition and infected with methicillin-resistant Staphylococcus aureus.
abstract: OBJECTIVE
  Nutritional aggression in critical periods may lead to epigenetic changes that affect gene expression. The aim of this study was to assess the effect of neonatal malnutrition on the expression of toll-like receptor (TLR)-2, TLR-4, and NLRP3 receptors, caspase-1 enzyme, and interleukin (IL)-1 β production in macrophages infected with methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) Staphylococcus aureus.
  
  
  METHODS
  Wistar rats (N = 24) were divided in two distinct groups: nourished (17% casein) and malnourished (8% casein). Four systems were established after the isolation of mononuclear cells: negative control, positive control, MRSA, and MSSA. The plates were incubated at 37°C for 24 h in humidified atmosphere and 5% carbon dioxide. Tests were performed after this period to analyze the expression of standard recognition receptors, caspase-1 enzyme, and the production of IL-1 β. Student's t test and analysis of variance were used in the statistical analysis; P < 0.05 was statistically significant.
  
  
  RESULTS
  Malnutrition reduced animal growth and the expression of TLR-2, TLR-4, and NLRP3 receptors, the caspase-1 enzyme, and the IL-1 β levels in macrophages infected with lipopolysaccharides in the present study. However, the interaction between the S. aureus and the macrophages promoted greater gene expression of receptors and enzymes.
  
  
  CONCLUSIONS
  The neonatal malnutrition model compromised the expression of standard recognition receptors, of the caspase-1 enzyme as well as the production of IL-1 β. However, the S. aureus and neonatal malnutrition combination led to intense transcription of such innate immunity components. Therefore, the deregulation in the expression of TLR and NLRP3 receptors and of the caspase-1 enzyme may induce extensive tissue injury and favor the permanence and spread of these bacteria, especially those that are methicillin resistant.
authors.affiliation: Laboratory of Immunopathology Keizo Asami, Federal University of Pernambuco, Pernambuco, Brazil. Electronic address: Natalia.morais@univasf.edu.br.
authors.forename: Natália
authors.initials: N
authors.lastname: Gomes de Morais
authors.affiliation: Department of Tropical Medicine, Federal University of Pernambuco, Pernambuco, Brazil.
authors.forename: Thacianna
authors.initials: T
authors.lastname: Barreto da Costa
authors.affiliation: Laboratory of Immunopathology Keizo Asami, Federal University of Pernambuco, Pernambuco, Brazil.
authors.forename: Joana Maria
authors.initials: JM
authors.lastname: Bezerra de Lira
authors.affiliation: Aggeu Magalhães Research Center, Oswaldo Cruz Foundation, Pernambuco, Brazil.
authors.forename: Suênia
authors.initials: S
authors.lastname: da Cunha Gonçalves de Albuquerque
authors.affiliation: Laboratory of Immunogenetics, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation, Pernambuco, Brazil.
authors.forename: Valéria Rêgo
authors.initials: VR
authors.lastname: Alves Pereira
authors.affiliation: Laboratory of Immunoparasitology, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation, Pernambuco, Brazil.
authors.forename: Milena
authors.initials: M
authors.lastname: de Paiva Cavalcanti
authors.affiliation: Federal University of Pernambuco, Pernambuco, Brazil.
authors.forename: Célia Maria
authors.initials: CM
authors.lastname: Machado Barbosa de Castro
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007774:Lactation; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D008297:Male; D044342:Malnutrition / Q000150:complications* / Q000178:diet therapy / Q000209:etiology; D039382:Maternal Nutritional Physiological Phenomena; D055624:Methicillin-Resistant Staphylococcus aureus / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000150:complications* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: C000594089:IL1B protein, rat; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D020170:Caspase 1
keywords: Infection; Inflammasome; MRSA; Macrophage; Malnutrition