TLR2 and TLR4 activity in monocytes and macrophages after exposure to amoxicillin, ciprofloxacin, doxycycline and erythromycin

Abstract

Background Antibiotics are used to treat bacterial infections but also impact immunity. This is usually attributed to antibiotic-induced dysbiosis of the microbiota, but antibiotics may have a direct effect on immune cells and immunity-associated receptors, such as Toll-like receptors (TLRs). Objectives To investigate whether antibiotics alter TLR2/1, TLR2/6 and TLR4 activity in immune cells. Methods We evaluated the effects of amoxicillin, ciprofloxacin, doxycycline and erythromycin on TLR2/1-, TLR2/6- and TLR4-induced NF-κB activation in THP1-XBlue™-MD2-CD14 cells. Furthermore, we studied TNF-α and IL-6 levels in THP-1-derived macrophages after exposure to these antibiotics and TLR ligands. Results Amoxicillin had no effect on any of the TLRs studied. However, ciprofloxacin reduced TLR2/1, TLR2/6 and TLR4 activity in THP1-XBlue™-MD2-CD14 cells and decreased TLR2/1-induced TNF-α and IL-6 in macrophages. Doxycycline reduced TLR2/6 and TLR4 activity in THP1-XBlue™-MD2-CD14 cells and TNF-α and IL-6 levels in response to TLR2/6 stimulation in macrophages. Erythromycin decreased TLR2/1 and TLR4 activity in THP1-XBlue™-MD2-CD14 cells without changes in TNF-α and IL-6 levels in macrophages. In addition, ciprofloxacin decreased the expression of TLR2 mRNA. Conclusions These results suggest that some antibiotics may attenuate TLR-dependent monocyte/macrophage responses and likely reduce bacterial clearance. The latter is particularly important in infections with AMR bacteria, where misprescribed antibiotics not only fail in control of AMR infections but might also weaken host defence mechanisms by limiting innate immune responses. Our data suggest that efforts should be made to prevent the deterioration of the immune response during and after antibiotic treatment.

Early antibiotics and risk for necrotizing enterocolitis in premature infants: A narrative review

“…It is also possible that antibiotics have direct effects on immune cells and immune-mediated receptors that can modify risk for NEC ( 97 , 98 ). For example, in vitro studies revealed that gentamicin, a first-line antibiotic drug of choice for neonatal sepsis, can directly inhibit the chemotactic response of human polymorphonuclear leukocytes ( 99 ).…”

A novel 12-membered ring non-antibiotic macrolide EM982 attenuates cytokine production by inhibiting IKKβ and IκBα phosphorylation

“…However, when we examined it from the same perspective, EM982 showed immunomodulatory activity toward all cell lines used in this study, whereas EM decreased cytokine production only in PMA-untreated THP-1 cells. Three previous studies have reported the effect of EM on cytokine production in THP-1 cells: EM inhibited IL6 transcription in PMA-untreated THP-1 cells by approximately 20% at the mRNA level ( 24 ), EM had no significant effect on TNF-α and IL-6 production in PMA-differentiated THP-1 cells at the protein level ( 25 ), and EM decreased IL-8 production in THP-1 cells differentiated with 1,25-dihydroxy vitamin D3 by approximately 60% at the protein level ( 26 ). These findings suggest that the effect of EM differs depending on the differentiation method even in the same cell type.…”

Anti‑obesity and immunostimulatory activity of Chrysosplenium flagelliferum in mouse preadipocytes 3T3‑L1 cells and mouse macrophage RAW264.7 cells

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