Abstract
BackgroundThe increasing resistance of Staphylococcus aureus to conventional antibiotics poses a major health problem. Moreover, S. aureus can survive within phagocytes, thus evading some antibiotics and the innate immune response. Rhodomyrtone, a bioactive compound from the leaves of Rhodomyrtus tomentosa, possesses potent antibacterial activity against methicillin-resistant S. aureus (MRSA). This study was to investigate the immunomodulatory effects of rhodomyrtone on THP-1 monocytes in response to MRSA.MethodsTHP-1 monocytes were stimulated with heat-killed MRSA, followed by treatment with rhodomyrtone. The cell pellets were prepared to detect pro-inflammatory molecules using real-time PCR. The supernatants were collected to assess nitric oxide production using Griess assay. Assays for phagocytosis and bacterial killing by THP-1 monocytes were performed to determine if they were affected by rhodomyrtone.ResultsExpression of pro-inflammatory molecules including IL-1β, TNF-α, IL-6, and iNOS was enhanced in THP-1 monocytes stimulated with high doses of heat-killed MRSA (108 to 109 cfu/ml). In contrast, monocytes stimulated with MRSA at lower doses (106 to 107 cfu/ml) did not induce the expression of these cytokines. However, rhodomyrtone significantly increased the expression of pro-inflammatory mediators, IL-6 and iNOS in monocytes stimulated with heat-killed MRSA at low doses, and displayed some anti-inflammatory activity by reducing TNF-α expression in monocytes stimulated with heat-killed MRSA at high doses. Treatment with rhodomyrtone also significantly up-regulated the expression of the key pattern recognition receptors, TLR2 and CD14, in THP-1 monocytes stimulated with heat-killed MRSA at 106 to 109 cfu/ml, while heat-killed MRSA alone did not induce the expression of these molecules. The ability of rhodomyrtone to eliminate MRSA from the monocytes was observed within 24 h after treatment.ConclusionRhodomyrtone enhanced the expression of pattern recognition receptors by monocytes in response to MRSA. Increased expression of these receptors might improve MRSA clearance by modulating pro- and anti-inflammatory cytokine responses.
Highlights
Methicillin-resistant strains of Staphylococcus aureus (MRSA) can express several potential virulence factors such as surface protein adhesins and toxins to invade and destroy host tissues
Rhodomyrtone enhances IL-6 and decreases tumor necrosis factor-alpha (TNF-a) expression in THP-1 monocytes stimulated with methicillin-resistant S. aureus (MRSA)
We stimulated THP-1 monocytes with heat-killed MRSA and found that monocytes stimulated with heat-killed MRSA at 108 to 109 cfu/ml increased their expression of interleukin-1 beta (IL-1b), TNF-a and IL-6 mRNA in a dose dependent manner (Figure 1)
Summary
Methicillin-resistant strains of Staphylococcus aureus (MRSA) can express several potential virulence factors such as surface protein adhesins and toxins to invade and destroy host tissues. The innate immune system plays an important role in host defense against pathogens, which it detects through specific pattern recognition receptors including toll-like receptors (TLR) and CD14 [4]. Monocytes produce proinflammatory molecules, such as tumor necrosis factor-alpha (TNF-a), interleukin-1 beta (IL-1b), IL-6, and nitric oxide (NO) to destroy pathogens [5]. These molecules play crucial roles in innate immune responses such as phagocytosis and pathogen clearance. The increasing resistance of Staphylococcus aureus to conventional antibiotics poses a major health problem. This study was to investigate the immunomodulatory effects of rhodomyrtone on THP-1 monocytes in response to MRSA
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