Abstract
Staphylococcus aureus is a Gram-positive bacterium that is considered an important human pathogen. Due to its virulence and ability to acquire mechanisms of resistance to antibiotics, the clinical severity of S. aureus infection is driven by inflammatory responses to the bacteria. Thus, the present study aimed to investigate the modulating role of citral in inflammation caused by S. aureus infection. For this, we used an isolate obtained from a nasal swab sample of a healthy child attending a day-care centre in Vitória da Conquista, Bahia, Brazil. The role of citral in modulating immunological factors against S. aureus infection was evaluated by isolating and cultivating human peripheral blood mononuclear cells. The monocytes were treated with 4%, 2%, and 1% citral before and after inoculation with S. aureus. The cells were analysed by immunophenotyping of monocyte cell surface molecules (CD54, CD282, CD80, HLA-DR, and CD86) and cytokine dosage (IL-1β, IL-6, IL-10, IL-12p70, IL-23, IFN-γ, TGF-β, and TNF-α), and evaluated for the expression of 84 genes related to innate and adaptive immune system responses. GraphPad Prism software and variables with P values < 0.05, were used for statistical analysis. Our data demonstrated citral’s action on the expression of surface markers involved in recognition, presentation, and migration, such as CD14, CD54, and CD80, in global negative regulation of inflammation with inhibitory effects on NF-κB, JNK/p38, and IFN pathways. Consequently, IL-1β, IL-6, IL-12p70, IL-23, IFN-γ, and TNF-α cytokine expression was reduced in groups treated with citral and groups treated with citral at 4%, 2%, and 1% and infected, and levels of anti-inflammatory cytokines such as IL-10 were increased. Furthermore, citral could be used as a supporting anti-inflammatory agent against infections caused by S. aureus. There are no data correlating citral, S. aureus, and the markers analysed here; thus, our study addresses this gap in the literature.
Highlights
Significant changes were observed between control group (CN) and LPS groups compared to infected group (INF) group in terms of the expression levels of CD86, CN, CIT2, CIT1, and treated and infected group (TI) groups at three concentrations for CD282, and CN, CIT4, TI4, TI2, and IT4 groups for HLA-DR
CIT groups at the three concentrations showed a significant difference in the levels of CD14, CD80, and CD282 compared to the CN group, CD54 compared to the INF and CN groups, and CD 86 compared to the CN and LPS groups
The infected and treated groups (IT) groups showed a significant difference in the number of monocytes compared to the INF, CN, LPS, CIT, and TI groups at the three concentrations for CD14, CD54, and CD80
Summary
CCR4 Chemokine (C–C motif) receptor 4 CCR5 Chemokine (C–C motif) receptor 5 CCR6 Chemokine (C–C motif) receptor 6 CCR8 Chemokine (C–C motif) receptor 8 CD14 CD14 molecule CD282 CD282 molecule CD4 CD4 molecule CD40 CD40 molecule, TNF receptor superfamily member 5 CD40LG CD40 ligand CD54 CD54 molecule CD80 CD80 molecule CD86 CD86 molecule CD8A CD8a molecule Cholesterol-HDL High-density lipoprotein cholesterol Cholesterol-LDL Low-density lipoprotein cholesterol CIT Treated groups CN Negative control group CRP C-reactive protein, pentraxin-related CSF2 Colony stimulating factor 2 (granulocyte–macrophage) CXCL10 Chemokine (C–X–C motif) ligand 10 CXCL8 Interleukin 8 CXCR3 Chemokine (C–X–C motif) receptor 3 DDX58 DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 ESKAPE Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa And Enterobacter species FASLG Fas ligand (TNF superfamily, member 6) FOXP3 Forkhead box P3 GAPDH Glyceraldehyde-3-phosphate dehydrogenase GATA3 GATA binding protein 3 HA-MRSA Hospital-acquired methicillin-resistant Staphylococcus aureus HLA-A Major histocompatibility complex, class I, A HLA-E Major histocompatibility complex, class I, E HPRT1 Hypoxanthine phosphoribosyltransferase 1 icaA Intercellular adhesion gene cluster type A icaD Intercellular adhesion gene cluster type A ICAM1 Intercellular adhesion molecule 1 ICU Intensive care unit IFNA1 Interferon, alpha 1 IFNAR1 Interferon (alpha, beta and omega) receptor 1 IFNB1 Interferon, beta 1, fibroblast IFNG Interferon, gamma IFNGR1 Interferon gamma receptor 1 IL10 Interleukin 10 IL-12p70 Interleukin IL13 Interleukin IL17A Interleukin 17A IL18 Interleukin 18 (interferon-gamma-inducing factor) IL1A Interleukin 1, alpha IL1B/IL-1β Interleukin 1, beta IL1R1 Interleukin 1 receptor, type I IL2 Interleukin 2 IL-23/IL23A Interleukin 23, alpha subunit p19 IL4 Interleukin 4 IL5 Interleukin 5 (colony-stimulating factor, eosinophil) IL-6/IL6 Interleukin 6 (interferon, beta 2) INF Infected group IRAK1 Interleukin-1 receptor-associated kinase 1 IRF3 Interferon regulatory factor 3 IRF7 Interferon regulatory factor 7 IT Infected and treated group ITGAM Integrin, alpha M (complement component 3 receptor 3 subunit) JAK2 Janus kinase 2 JNK/p38 Mammalian stress-activated protein kinases p38 and JNK LPS Lipopolysaccharides LY96 Lymphocyte antigen 96 LYZ Lysozyme MAPK1 Mitogen-activated protein kinase 1 MAPK8 Mitogen-activated protein kinase 8 MBL2 Mannose-binding lectin (protein C) 2, soluble. Staphylococcus aureus is a coccus-shaped, Gram-positive bacterium belonging to the group of pathogens referred to as ‘ESKAPE’ (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) It is considered an important human pathogen that is linked to a wide range of clinical manifestations, including respiratory infections, septic arthritis, endocarditis, and toxic shock syndrome[1,2,3]. Monocytes are antigen-presenting cells, and their expression of different cell-surface markers plays important roles in the infectious process or in disease remission Their activation is necessary for initiating modulation of immune responses through gene transcription related to different pathways, including nuclear factor kappa B (NF-κB), leading to the production and secretion of proinflammatory mediators and c ytokines[16]. The adequate production of inflammatory mediators aims to eliminate infection by m icroorganisms[19]
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