Open AccessModulation of cytokine production and enhancement of cell viability by TLR7 and TLR9 ligands during anthrax infection of macrophages
Author(s) -
Sabet Mojgan,
Cottam Howard B.,
Guiney Donald G.
Publication year - 2006
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2006.00096.x
Subject(s) - bacillus anthracis , biology , microbiology and biotechnology , tlr7 , cytokine , tumor necrosis factor alpha , tlr9 , macrophage , toll like receptor , immunology , innate immune system , immune system , in vitro , bacteria , biochemistry , gene expression , genetics , dna methylation , gene
Inhalation of Bacillus anthracis , a bioterrorism agent, results in a high mortality rate despite appropriate antibiotic therapy. Macrophages appear to be a key factor in B. anthracis pathogenesis. The burst of pro‐inflammatory cytokines from macrophages could be a major cause of death in anthrax. However, preactivation of Toll‐like receptors (TLRs) could modify the host response. TLR ligands stimulate the release of activating cytokines but may also down‐modulate the subsequent deleterious cytokine response to pathogens. We developed a cell culture model to measure macrophage responses to B. anthracis spores and bacilli. We found that germination from spores to bacilli produced a substantial stimulus for the secretion of the cytokines IL‐6, TNF‐α, IL‐10, and IL‐12 p40. Our studies showed that pretreatment of mouse macrophages with the TLR9 ligand ISS‐1018, or the TLR7 ligands R‐848 and IT‐37, results in a substantial decrease in the subsequent secretion of IL‐6 and TNF‐α in response to B. anthracis infection of macrophages. Furthermore, the TLR7 and TLR9 ligands significantly decreased anthrax‐induced cytotoxicity in the macrophages. These findings suggest that TLR ligands may contribute to the enhancement of innate immunity in B. anthracis infection by suppressing potentially deleterious pro‐inflammatory cytokine responses and by improving macrophage viability.