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 Plus annual

Presents the access of premium content as premium feature

Premium Content

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 annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

UNC93B1 associates with Toll-Like Receptor (TLR) 3, TLR7 and TLR9, mediating their translocation from the endoplasmic reticulum to the endolysosome, hence allowing proper activation by nucleic acid ligands. We found that the triple deficient ‘3d’ mice, which lack functional UNC93B1, are hyper-susceptible to infection with  Toxoplasma gondii . We established that while mounting a normal systemic pro-inflammatory response,  i.e.  producing abundant MCP-1, IL-6, TNFα and IFNγ, the 3d mice were unable to control parasite replication. Nevertheless, infection of reciprocal bone marrow chimeras between wild-type and 3d mice with  T. gondii  demonstrated a primary role of hemopoietic cell lineages in the enhanced susceptibility of  UNC93B1  mutant mice. The protective role mediated by UNC93B1 to  T. gondii  infection was associated with impaired IL-12 responses and delayed IFNγ by spleen cells. Notably, in macrophages infected with  T. gondii , UNC93B1 accumulates on the parasitophorous vacuole. Furthermore, upon  in vitro  infection the rate of tachyzoite replication was enhanced in non-activated macrophages carrying mutant  UNC93B1  as compared to wild type gene. Strikingly, the role of UNC93B1 on intracellular parasite growth appears to be independent of TLR function. Altogether, our results reveal a critical role for UNC93B1 on induction of IL-12/IFNγ production as well as autonomous control of  Toxoplasma  replication by macrophages.

UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii