Toll-like receptor 2 downregulation and cytokine dysregulation predict mortality in patients with Staphylococcus aureus bacteremia

• Published in: BMC infectious diseases Vol. 20; no. 1; p. 901
• Main Authors: Kim, Nak-Hyun, Sung, Ji Yeon, Choi, Yoon Jung, Choi, Su-Jin, Ahn, Soyeon, Ji, Eunjeong, Kim, Moonsuk, Kim, Chung Jong, Song, Kyoung-Ho, Choe, Pyoeng Gyun, Park, Wan Beom, Kim, Eu Suk, Park, Kyoung Un, Kim, Nam-Joong, Oh, Myoung-Don, Kim, Hong Bin
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.11.2020; BioMed Central; BMC
• Subjects: Adult; Age; Aged; Aged, 80 and over; Antibiotics; Bacteremia; Bacteremia - metabolism; Bacteremia - mortality; Causes of; Chemokines; Clinical outcomes; Cytokines; Cytokines - analysis; Cytokines - metabolism; Demographics; Down-Regulation - genetics; Electrochemiluminescence; Female; Gene expression; Health aspects; Health care facilities; Humans; Immune response; Immune system; Infectious diseases; Interleukin 10; Interleukin 6; Interleukins; Male; Middle Aged; Mortality; mRNA; Pathogens; Patient outcomes; Patients; Prognosis; Prospective Studies; Proteins; Real-Time Polymerase Chain Reaction; Receptors; RNA, Messenger - genetics; Sepsis; Software; Standard deviation; Staphylococcal Infections - metabolism; Staphylococcal Infections - microbiology; Staphylococcal Infections - mortality; Staphylococcus aureus; Staphylococcus aureus - isolation & purification; Staphylococcus aureus - metabolism; Staphylococcus infections; Survival; Survivors; Tertiary Care Centers; TLR2; TLR2 protein; Toll-like receptor 2 (TLR2); Toll-Like Receptor 2 - genetics; Toll-like receptors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; South Korea; United States > US; Toll-like receptor 2 (TLR2); Cytokines; Bacteremia; Staphylococcus aureus
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-020-05641-z

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. 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. 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/TNF-α ratios than the survivors did (P = 0.007). 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.