Biology subjects

Reid, A. M.

Publications and source records attributed to Reid, A. M..

3 recordsLinked to original sources

bioRxiv2025

Quantifying maternal antibody transfer to colostrum and cord blood reveals virus-specific selectivity in dogs

BackgroundNeonatal infections are a leading cause of mortality in dogs, with up to 30% of puppies dying within the first three weeks of life. During this period of immune development, protection is highly dependent on maternal antibodies (MatAbs) transferred across the placenta and via colostrum. Despite the critical importance of this transfer, little is known about the biological or clinical factors that determine its magnitude, whether specific antibodies are preferentially transferred, or how these processes vary across a broad population of dogs. MethodsTo quantify and explore the determinants of MatAb transfer in dogs, we analyzed matched maternal serum, cord blood, and colostrum samples collected from 44 client-owned dams undergoing cesarean section at a university veterinary hospital. Total IgG and virus-specific antibodies against canine parvovirus (CPV) and canine distemper virus (CDV) were analyzed. We also evaluated the influence of maternal factors, including age, breed, body weight, parity and litter size on MatAb transfer efficiency. ResultsAcross this diverse population, we observed limited transplacental transfer of MatAbs (4.5-6% maternal titer), in agreement with previous studies and as expected with the endotheliochorial placenta of dogs. In contrast, virus-specific IgG was highly enriched in colostrum, with 10.7-fold (CPV) and 8.1-fold (CDV) increases relative to serum. Transfer efficiency was significantly greater for virus-specific antibodies than for total IgG (3.2-fold), suggesting selective enrichment of antiviral antibodies during colostrogenesis. Maternal serum antibody titer emerged as the primary factor influencing the efficiency of antibody transfer. ConclusionsThese findings provide the most comprehensive quantification to date of MatAb transfer routes in dogs, revealing preferential transfer of virus-specific IgG to colostrum and highlighting the crucial role of colostrum intake for neonatal immunity. This work establishes a foundation for identifying antibody characteristics that influence MatAb transfer efficiency and reiterates the importance of ensuring dams have adequate titers of virus-specific IgG prior to breeding.

immunology↗

bioRxiv2024

Dendritic cells type 1 control the formation, maintenance, and function of tertiary lymphoidstructures in cancer

Tertiary lymphoid structures (TLS) are organized immune cell aggregates that arise in chronic inflammatory conditions. In cancer, TLS are associated with better prognosis and enhanced response to immunotherapy, making these structures attractive therapeutic targets. However, the mechanisms regulating TLS formation and maintenance in cancer are incompletely understood. Using spatial transcriptomics and multiplex imaging across various human tumors, we found an enrichment of mature dendritic cells (DC) expressing high levels of CCR7 in TLS, prompting us to investigate the role of DC in the formation and maintenance of TLS in solid tumors. To address this, we developed a novel murine model of non-small cell lung cancer (NSCLC) that forms mature TLS, containing B cell follicles with germinal centers and T cell zones with T follicular helper cells (TFH) and TCF1+PD-1+ progenitor exhausted CD8+ T cells (Tpex). Here we show that, during the early stages of tumor development, TLS formation relies on IFN{gamma}-driven maturation of the conventional DC type 1 (cDC1) subset, their migration to tumor-draining lymph nodes (tdLN), and recruitment of activated T cells to the tumor site. As tumors progress, TLS maintenance becomes independent of T cell egress from tdLN, coinciding with a significant reduction of cDC1 migration to tdLN. Instead, mature cDC1 accumulate within intratumoral CCR7 ligand-enriched stromal hubs. Notably, timed depletion of cDC1 or disruption of their migration to these stromal hubs after TLS are formed alters TLS maintenance. Importantly, we found that cDC1-mediated antigen presentation to both CD4+ and CD8+ T cells and intact CD40 signaling, is critical for the maintenance of TLS, the preservation of the TFH cell pool, the formation of germinal center and the production of tumor-specific IgG antibodies. These findings underscore the key role of mature cDC1 in establishing and maintaining functional TLS within tumor lesions and highlight the potential for cDC1-targeting therapies as a promising strategy to enhance TLS function and improve anti-tumor immunity in patients with cancer.

immunology↗

bioRxiv2017

Centromeric DNA destabilizes H3 nucleosomes to promote CENP-A deposition during the cell cycle

Active centromeres are defined by the presence of nucleosomes containing CENP-A, a histone H3 variant, which alone is sufficient to direct kinetochore assembly. Once assembled at a location CENP-A chromatin and kinetochores are maintained at that location though a positive feedback loop where kinetochore proteins recruited by CENP-A itself promote deposition of new CENP-A following replication. Although CENP-A chromatin itself is a heritable entity, it is normally associated with specific sequences. Intrinsic properties of centromeric DNA may favour the assembly of CENP-A rather than H3 nucleosomes. Here we investigate histone dynamics on centromeric DNA. We show that during S-phase histone H3 is deposited as a placeholder at fission yeast centromeres and is subsequently evicted in G2 when we detect deposition of the majority of new CENP-ACnp1. We also find that centromeric DNA has an innate property of driving high rates of turnover of H3 containing nucleosomes resulting in low nucleosome occupancy. When placed at an ectopic chromosomal location in the absence of any CENP-ACnp1 assembly, centromeric DNA retains its ability to impose S-phase deposition and G2 eviction of H3, suggesting that features within this DNA program H3 dynamics. As RNAPII occupancy on this centromere DNA coincides with H3 eviction in G2, we propose a model in which RNAPII-coupled chromatin remodelling promotes replacement of H3 with CENP-ACnp1 nucleosomes.

cell biology↗