Toll-like receptor 2 downregulation and cytokine dysregulation predict mortality in patients with Staphylococcus aureus
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RESEARCH ARTICLE
Open Access
Toll-like receptor 2 downregulation and cytokine dysregulation predict mortality in patients with Staphylococcus aureus bacteremia Nak-Hyun Kim1,2†, Ji Yeon Sung3,4†, Yoon Jung Choi2, Su-Jin Choi1, Soyeon Ahn5, Eunjeong Ji5, Moonsuk Kim2, Chung Jong Kim2,6, Kyoung-Ho Song2, Pyoeng Gyun Choe1, Wan Beom Park1, Eu Suk Kim2, Kyoung Un Park3, Nam-Joong Kim1, Myoung-don Oh1 and Hong Bin Kim2*
Abstract Background: Staphylococcus aureus bacteremia (SAB) presents heterogeneously, owing to the differences in underlying host conditions and immune responses. Although Toll-like receptor 2 (TLR2) is important in recognizing S. aureus, its function during S. aureus infection remains controversial. We aimed to examine the association of TLR2 expression and associated cytokine responses with clinical SAB outcomes. Methods: Patients from a prospective SAB cohort at two tertiary-care medical centers were enrolled. Blood was sampled at several timepoints (≤5 d, 6–9 d, 10–13 d, 14–19 d, and ≥ 20 d) after SAB onset. TLR2 mRNA levels were determined via real-time PCR and serum tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-10 levels were analyzed with multiplex-high-sensitivity electrochemiluminescent ELISA. Results: TLR2 levels varied among 59 SAB patients. On days 2–5, TLR2 levels were significantly higher in SAB survivors than in healthy controls (p = 0.040) and slightly but not significantly higher than non-survivors (p = 0.120), and SAB patients dying within 7 d had lower TLR2 levels than survivors (P = 0.077) although statistically insignificant. IL-6 and IL-10 levels were significantly higher in non-survivors than in survivors on days 2–5 post-bacteremia (P = 0.010 and P = 0.021, respectively), and those dying within 7 d of SAB (n = 3) displayed significantly higher IL-10/TNFα ratios than the survivors did (P = 0.007). Conclusion: TLR2 downregulation and IL-6 and IL-10 concentrations suggestive of immune dysregulation during early bacteremia may be associated with mortality from SAB. TLR2 expression levels and associated cytokine reactions during early-phase SAB may be potential prognostic factors in SAB, although larger studies are warranted. Keywords: Staphylococcus aureus, Bacteremia, Toll-like receptor 2 (TLR2), Cytokines
* Correspondence: [email protected] † Nak-Hyun Kim and Ji Yeon Sung contributed equally to this work. 2 Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 173 Gumi-ro, Bundang-gu, Seongnam 463-707, Republic of Korea Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party ma
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