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Ageing affects the CD4+ T cell polarization and mucosal tropism induced by TLR2...

Zúquete, Sara; Ferreira, Mariana; Delgado, Inês L.; Rosa, Maria teresa; Mendes, Ana Catarina; Santos, Dulce; Nolasco, Sofia; Graça, Luís

Toll-like receptor (TLR)2 activation induces aldehyde dehydrogenase enzymes in non-mucosal dendritic cells (DCs), enabling them to metabolize vitamin A into all-trans retinoic acid, which induces the expression of mucosal-homing molecules (α4β7 and CCR9) in the activated T cells. Recently, we have shown that the simultaneous activation of non-mucosal DCs through TLR2 and TLR4 maintains such capacity while reinf...


Balancing act: tubulin glutamylation and microtubule dynamics in Toxoplasma gondii

Delgado, Inês; Gonçalves, João; Fernandes, Rita; Zúquete, Sara; Basto, Afonso P.; Leitão, Alexandre; Soares, Helena; Nolasco, Sofia

The success of the intracellular parasite Toxoplasma gondii in invading host cells relies on the apical complex, a specialized microtubule cytoskeleton structure associated with secretory organelles. The T. gondii genome encodes three isoforms of both α- and β-tubulin, which undergo specific post-translational modifications (PTMs), altering the biochemical and biophysical proprieties of microtubules and modulat...


Balancing act: tubulin glutamylation and microtubule dynamics in Toxoplasma gondii

Delgado, Inês L.S.; Gonçalves, João; Fernandes, Rita; Zúquete, Sara; Basto, Afonso P.; Leitão, Alexandre; Soares, Helena; Nolasco, Sofia

The success of Toxoplasma gondii (intracellular parasite) host cell invasion relies on the apical complex, a specialized microtubule cytoskeleton structure associated with secretory organelles. The genome encodes three isoforms of both α- and β-tubulin which are altered by specific post-translational modifications (PTMs), changing the biochemical/biophysical proprieties of microtubules, and modulating their int...


Combined TLR2/TLR4 activation equip non-mucosal dendritic cells to prime Th1 ce...

Zúquete, Sara; Ferreira, Mariana; Delgado, Inês L. S.; Gazalle, Paula; Andaluz, Stephanie; Rosa, Maria Teresa; Mendes, Ana Catarina; Santos, Dulce

Activated CD4+ T cells located at mucosal surfaces orchestrate local effector immune mechanisms. When properly polarized, these cells contribute to block infections at early stages and may be essential to restrain the local growth of mucosal tumors, playing a critical role in host protection. How CD4+ T cells simultaneously integrate gut-homing instructions and Th polarization signals transmitted by TLR-activat...


The apicomplexan parasite Toxoplasma gondii

Delgado, Inês L. S.; Zúquete, Sara; Santos, Dulce; Basto, Afonso P.; Leitão, Alexandre; Nolasco, Sofia

Toxoplasma gondii is a ubiquitous zoonotic parasite with an obligatory intracellular lifestyle. It relies on a specialized set of cytoskeletal and secretory organelles for host cell invasion. When infecting its felid definitive host, T. gondii undergoes sexual reproduction in the intestinal epithelium, producing oocysts that are excreted with the feces and sporulate in the environment. In other hosts and/or tis...


Characterization of a MOB1 homolog in the Apicomplexan parasite toxoplasma gondii

Delgado, Inês L. S.; Tavares, Alexandra; Francisco, Samuel; Santos, Dulce; Coelho, João; Basto, Afonso P.; Zúquete, Sara; Müller, Joachim

Monopolar spindle One Binder1 (MOB1) proteins are conserved components of the tumor-suppressing Hippo pathway, regulating cellular processes such as cytokinesis. Apicomplexan parasites present a life cycle that relies on the parasites’ ability to differentiate between stages and regulate their proliferation; thus, Hippo signaling pathways could play an important role in the regulation of the apicomplexan life c...


Micro RNAs in Tfh regulation : small molecules with a big impact

Basto, Afonso P.; Graca, Luis

ABSTRACT - The germinal center (GC) reactions are critical for the production of high-affinity antibodies that comprise the protective humoral response elicited by infection or vaccination. GCs are initiated through the interaction of B cells with T follicular helper (Tfh) cells. While the transcriptional regulation of Tfh differentiation has been studied in great detail, the impact of micro RNAs (miRNAs) on Tf...


Peptidylprolyl isomerase C (Ppic) regulates invariant Natural Killer T cell (iN...

Paiva, Ricardo S.; Ramos, Camila V.; Azenha, Sara R.; Alves, Carolina; Basto, Afonso P.; Graça, Luís; Martins, Vera C.

Peptidyl-prolyl cis-trans isomerase C (Ppic) is expressed in several bone marrow (BM) hematopoietic progenitors and in T-cell precursors. Since the expression profile of Ppic in the hematoimmune system was suggestive that it could play a role in hematopoiesis and/or T lymphocyte differentiation, we sought to test that hypothesis in vivo. Specifically, we generated a Ppic-deficient mouse model by targeting the e...


A new cloning system based on the OprI lipoprotein for the production of recomb...

Basto, Afonso P.; Piedade, João; Ramalho, Ruben; Alves, Susana; Soares, Helena; Cornelis, Pierre; Martins, Carlos; Leitão, Alexandre

The conjugation of antigens with ligands of pattern recognition receptors (PRR) is emerging as a promising strategy for the modulation of specific immunity. Here, we describe a new Escherichia coli system for the cloning and expression of heterologous antigens in fusion with the OprI lipoprotein, a TLR ligand from the Pseudomonas aeruginosa outer membrane (OM). Analysis of the OprI expressed by this system reve...


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