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Differential Constitutive and Cytokine-Modulated Expression of Human Toll-like Receptors in Primary Neutrophils, Monocytes, and Macrophages
Article Number: SIS943278AI201222
20th December, 2022
Author(s):
D. Shane O’Mahony 1, Uyenvy Pham 1, Ramesh Iyer 1, Thomas R. Hawn 1, W. Conrad Liles 1,2,3
Abstract:
Human Toll-like receptors (TLRs) comprise a family of proteins that recognizes pathogen-associated molecular patterns (PAMPs) and initiates host innate immune responses. Neutrophils, monocytes, and macrophages are
critical cellular components of the human innate immune system. Proinflammatory cytokines, such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macro- phage colony-stimulating factor (M-CSF), and interferon-γ (IFN-γ), have been shown to up-regulate microbicidal
activity in these effector cells of innate immunity. Currently, the cellular and molecular mechanisms responsible
for these effects are not completely understood. We hypothesized that these cytokines may up-regulate TLR ex- pression as a mechanism to facilitate microbial recognition and augment the innate immune response. Using
quantitative realtime rt-PCR technology, we examined constitutive expression of TLR2, TLR4, TLR5, and TLR9
mRNA and the effects of G-CSF, GM-CSF, M-CSF, and IFN-γ on TLR mRNA expression in purified populations of normal human neutrophils, monocytes, and monocyte-derived macrophages. Relative constitutive expression
of TLR2, TLR4, and TLR9 was similar in neutrophils and monocytes. Constitutive expression of TLR5 was less in neutrophils compared to monocytes. Constitutive expression of TLR4 was greater and that of TLR9 lower in
monocyte-derived macrophages compared to monocytes. Of the cytokines examined, IFN-γ and GM-CSF caused
the greatest effects on TLR expression. IFN- γ up-regulated TLR2 and TLR4 in neutrophils and monocytes.
GM-CSF up-regulated expression of TLR2 and TLR4 in neutrophils and TLR2 in monocytes. TLR5 was
down-regulated by inflammatory cytokines in monocytes. These results suggest a potential role for IFN- γ
and/or GM-CSF as therapeutic immunomodulators of the host defense to infection