Biology subjects

Posada, J.

Publications and source records attributed to Posada, J..

3 recordsLinked to original sources

bioRxiv2024

The GPI sidechain of Toxoplasma gondii prevents parasite pathogenesis

Glycosylphosphatidylinositols (GPIs) are highly conserved anchors for eukaryotic cell surface proteins. The apicomplexan parasite, Toxoplasma gondii, is a widespread intracellular parasite of warm-blooded animals whose plasma membrane is covered with GPI-anchored proteins, and free GPIs called GIPLs. While the glycan portion is conserved, species differ in sidechains added to the triple mannose core. The functional significance of the Glc1,4GalNAc{beta}1-sidechain reported in Toxoplasma gondii has remained largely unknown without an understanding of its biosynthesis. Here we identify and disrupt two glycosyltransferase genes and confirm their respective roles by serology and mass spectrometry. Parasites lacking the sidechain on account of deletion of the first glycosyltransferase, PIGJ, exhibit increased virulence during primary and secondary infections, suggesting it is an important pathogenesis factor. Cytokine responses, antibody recognition of GPI-anchored SAGs, and complement binding to PIGJ mutants are intact. In contrast, the scavenger receptor CD36 shows enhanced binding to PIGJ mutants, potentially explaining a subtle tropism for macrophages detected early in infection. Galectin-3, which bind GIPLs, exhibits a slight enhancement of binding to PIGJ mutants, and the protection of galectin-3 knockout mice from lethality suggests that{Delta} pigj parasite virulence in this context is sidechain dependent. Parasite numbers are not affected by{Delta} pigj early in the infection in wildtype mice, suggesting a breakdown of tolerance. However, increased tissue cysts in the brains of mice infected with{Delta} pigj parasites indicate an advantage over wildtype strains. Thus, the GPI sidechain of T. gondii plays a crucial and diverse role in regulating disease outcome in the infected host. SummaryThe functional significance of sidechain modifications to the GPI anchor is yet to be determined because the glycosyltransferases responsible for these modifications have not been identified. Here we present identification and characterization of both T. gondii GPI sidechain-modifying glycosyltransferases. Removal of the glycosyltransferase that adds the first GalNAc to the sidechain results in parasites without a sidechain on the GPI, and increased parasite virulence. Loss of the second glycosyltransferase results in a sidechain with GalNAc alone, and no glucose added, and has negligible effect on parasite virulence. This indicates GPI sidechains as fundamental to host-parasite interactions.

microbiology↗

bioRxiv2022

Fetal hematopoietic stem cells are activated during acute prenatal infection with Toxoplasma gondii and IFNγ

Infection directly influences adult hematopoietic stem cell (HSC) function and differentiation, but much less is known about the fetal hematopoietic response to infection during pregnancy. Here, we investigated the fetal hematopoietic response to maternal infection with Toxoplasma gondii (T. gondii), an intracellular parasite that elicits Type II IFN{gamma}-mediated maternal immunity. The effects of maternal IFN{gamma} on developing HSCs and the signals that mediate these interactions have not been investigated. Our investigation reveals that the fetal HSCs respond to T. gondii infection with virulence-dependent changes in proliferation, self-renewal potential, and lineage output. We demonstrate that maternal IFN{gamma} crosses the fetal-maternal interface and is perceived by fetal HSCs. By comparing the effects of maternal IFN{gamma} injection with maternal T. gondii infection, our observations reveal that IFN{gamma} mimics aspects of the fetal HSC response to infection. Moreover, our data disentangle the role of infection-induced inflammatory cytokines in driving the expansion of downstream hematopoietic progenitors. Our findings illuminate that the fetal HSC response to prenatal infection is distinct from the adult HSC response to IFN{gamma}-induced inflammation.

immunology↗

bioRxiv2021

Non-structural carbohydrate concentrations in woody organs, but not leaves, of temperate and tropical tree angiosperms are independent of the "fast-slow" plant economic spectrum

Background and AimsCarbohydrate reserves play a vital role in plant survival during periods of negative carbon balance. Considering active storage of reserves, there is a trade-off between carbon allocation to growth and to reserves and defense. A resulting hypothesis is that allocation to reserves exhibits a coordinated variation with functional traits associated with the fast-slow plant economics spectrum. MethodsWe tested the relationship between non-structural carbohydrates (NSC) of tree organs and functional traits using 61 angiosperm tree species from temperate and tropical forests with phylogenetic hierarchical Bayesian models. Key ResultsOur results provide evidence that NSC concentrations in woody organs and plant functional traits are largely decoupled, meaning that species resilience is unrelated to their position on the fast-slow plant economics spectrum. In contrast, we found that variation between NSC concentrations in leaves and the fast-slow continuum was coordinated, as species with higher leaf NSC had traits values associated with resource conservative species such as lower SLA, lower Amax, and high wood density. We did not detect an influence of leaf habit on the variation of NSC concentrations in tree organs. ConclusionsEfforts to predict the response of ecosystems to global change will need to integrate a suite of plant traits, such as NSC concentrations in woody organs, that are independent of the fast-slow spectrum and that capture how species respond to a broad range of global change factors.

plant biology↗