English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Reports implicating important roles for cholesterol and cholesterol-rich lipid rafts in host-pathogen interactions have largely employed sterol sequestering agents and biosynthesis inhibitors. Because the pleiotropic effects of these compounds can complicate experimental interpretation, we developed a new model system to investigate cholesterol requirements in pathogen infection utilizing DHCR24 −/−  mouse embryonic fibroblasts (MEFs). DHCR24 −/−  MEFs lack the Δ24 sterol reductase required for the final enzymatic step in cholesterol biosynthesis, and consequently accumulate desmosterol into cellular membranes. Defective lipid raft function by DHCR24 −/−  MEFs adapted to growth in cholesterol-free medium was confirmed by showing deficient uptake of cholera-toxin B and impaired signaling by epidermal growth factor. Infection in the absence of cholesterol was then investigated for three intracellular bacterial pathogens:  Coxiella burnetii ,  Salmonella enterica  serovar Typhimurium, and  Chlamydia trachomatis . Invasion by  S.  Typhimurium and  C. trachomatis  was unaltered in DHCR24 −/−  MEFs. In contrast,  C. burnetii  entry was significantly decreased in −cholesterol MEFs, and also in +cholesterol MEFs when lipid raft-associated α V β 3  integrin was blocked, suggesting a role for lipid rafts in  C. burnetii  uptake. Once internalized, all three pathogens established their respective vacuolar niches and replicated normally. However, the  C. burnetii -occupied vacuole within DHCR24 −/−  MEFs lacked the CD63-postive material and multilamellar membranes typical of vacuoles formed in wild type cells, indicating cholesterol functions in trafficking of multivesicular bodies to the pathogen vacuole. These data demonstrate that cholesterol is not essential for invasion and intracellular replication by  S.  Typhimurium and  C. trachomatis , but plays a role in  C. burnetii -host cell interactions.

Bacterial Colonization of Host Cells in the Absence of Cholesterol