A concretização do projeto na Lousã resultou da colaboração entre o Município da Lousã, através dos Serviços Municipais de Proteção Civil, os Baldios de Serpins e a Junta de Freguesia de Serpins. [soc...

SERPINE1 and SERPINB2-driven fibrin-rich niches locally programme immunosuppressive macrophages and exclude T cells, enabling spatially organized immune evasion in pancreatic ductal carcinoma.

A operação do Metrobus no percurso entre Lousã e Serpins (Estação) será retomada no dia 1 de setembro, de acordo com a informação divulgada pela Metro Mondego. A retoma permitirá restabelecer a ligaçã...

The kinase RIPK3 suppresses pathologic neuroinflammation in mouse models of flavivirus infection.

Tick serine protease inhibitors (serpins) are critical for tick feeding success and pathogen transmission. We previously demonstrated that two unique serpins, S12c5 and S13c5, are tandemly duplicated on Ixodes scapularis chromosome 5 and are injected into the host at heightened levels during feeding by Borrelia burgdorferi (Bb)-infected nymphs. Here, we characterize the biochemical properties and immunomodulatory functions of these serpins and investigate their roles in promoting Bb transmission. Despite their response to Bb infection, S12c5 and S13c5 share less than 20% overall amino acid identity and differ critically at their reactive center loop (RCL) P1 site, which determines substrate specificity: S13c5 contains a basic arginine residue, while S12c5 contains a polar serine residue. Consistent with these differences, recombinant S13c5 efficiently inhibited innate immune proteases including fXa, plasmin, and trypsin IV (SI: 2.5, 1.9, and 1.0; ka: 8.56 × 10³, 3.97 × 10⁵, and 1.08 × 10⁵ M⁻¹s⁻¹, respectively), and consequently delayed plasma clotting via the common pathway, whereas rS12c5 did not inhibit these proteases. However, despite molecular modeling predicting stronger interactions between S13c5 and complement proteases, both serpins inhibited MBL-pathway complement activation by targeting MASP1/3. Deletion of the RCL domain abolished this inhibitory activity, confirming both proteins function as typical inhibitory serpins. Functionally, rS13c5 enhanced Bb colonization in C3H mouse organs. Interestingly, immune response assays revealed a trade-off: S13c5, despite its broader inhibitory activity, was less immunogenic than S12c5. Collectively, these findings establish S12c5 and S13c5 as Bb transmission factors that promote spirochete survival through disruption of host innate immunity.

Tick serine protease inhibitors (serpins) are critical for tick feeding success and pathogen transmission. We previously demonstrated that two unique serpins, S12c5 and S13c5, are tandemly duplicated on Ixodes scapularis chromosome 5 and are injected into the host at heightened levels during feeding by Borrelia burgdorferi (Bb)-infected nymphs. Here, we characterize the biochemical properties and immunomodulatory functions of these serpins and investigate their roles in promoting Bb transmission. Despite their response to Bb infection, S12c5 and S13c5 share less than 20% overall amino acid identity and differ critically at their reactive center loop (RCL) P1 site, which determines substrate specificity: S13c5 contains a basic arginine residue, while S12c5 contains a polar serine residue. Consistent with these differences, recombinant S13c5 efficiently inhibited innate immune proteases including fXa, plasmin, and trypsin IV (SI: 2.5, 1.9, and 1.0; ka: 8.56 × 10³, 3.97 × 10⁵, and 1.08 × 10⁵ M⁻¹s⁻¹, respectively), and consequently delayed plasma clotting via the common pathway, whereas rS12c5 did not inhibit these proteases. However, despite molecular modeling predicting stronger interactions between S13c5 and complement proteases, both serpins inhibited MBL-pathway complement activation by targeting MASP1/3. Deletion of the RCL domain abolished this inhibitory activity, confirming both proteins function as typical inhibitory serpins. Functionally, rS13c5 enhanced Bb colonization in C3H mouse organs. Interestingly, immune response assays revealed a trade-off: S13c5, despite its broader inhibitory activity, was less immunogenic than S12c5. Collectively, these findings establish S12c5 and S13c5 as Bb transmission factors that promote spirochete survival through disruption of host innate immunity.

This study successfully determined the crystal structure of human serpin B9 at 1.9 Å resolution and identified notable structural differences surrounding helix D, providing a potential target for the development of anticancer therapeutics.

YouTube video by ruicp

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