GSE143619 Hydrogen sulfide dysregulates the immune response by suppressing central carbon metabolism to promote tuberculosis

Contributors : Md A Rahman ; Bridgette M Cumming ; Kelvin Addicot ; Hayden Pacl ; Shannon Russell ; Kievershen Nargan ; Threnesan Naidoo ; Pratistadevi K Ramdial ; John H Adamson ; Rui Wang ; Adrie J SteynSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe ubiquitous gasotransmitter hydrogen sulfide (H2S) has been recognised to play a crucial role in human health. However, a role for host H2S in pathogenesis has not yet been demonstrated. Using cystathionine -lyase (CSE) deficient mice, we demonstrated an unexpected role of H2S in Mtb pathogenesis. We showed that Mtb-infected CSE-/- mice survive longer than wild-type mice, and support reduced pathology and lower bacterial burdens in the lung, spleen and liver. Similarly, in vitro Mtb infection of m acrophages resulted in reduced colony forming units (CFUs) in CSE-/-cells. Chemical complementation of infected wild-type and CSE-/-macrophages using the slow H2S releaser GYY3147 and the CSE inhibitor DL-propargylglycine demonstrated that H2S is the effector molecule regulating Mtb survival in mac rophages. Furthermore, we demonstrate that CSE promotes an excessive innate immune response, suppresses the adaptive immune response and reduces circulating IL1β, IL-6, TNFα, and IFN-γ levels in response to Mtb infection. Notably, Mtb infected CSE-/- macrophages show increased flux through glyc olysis and the pentose phosphate pathway thereby establishing a critical link between ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research