Biology subjects

Patatsos, K.

Publications and source records attributed to Patatsos, K..

4 recordsLinked to original sources

bioRxiv2026

Attenuated interferon signalling in alveolar epithelium limits resistance to Streptococcus pyogenes

The upper respiratory tract is a primary niche for Streptococcus pyogenes colonisation and disease. Lower respiratory tract infection (pneumonia) is the most common invasive S. pyogenes syndrome. Studies have not previously examined how epithelial cells, from the airway to the alveolus, respond to S. pyogenes infection. Here, we established a scalable human in vitro model by differentiating induced pluripotent stem cells (iPSCs) into mature pseudostratified airway epithelium or alveolar type 2 epithelial cells, cultured at air-liquid interface and infected with S. pyogenes (M1UK and M75 strains). Both strains attached to iPSC-derived lung epithelial cells, with significantly greater adherence to the airway epithelium by M75 compared to M1UK. Moreover, invasion by both S. pyogenes strains of alveolar epithelial cells was greater than for the airway epithelium. Dynamic S. pyogenes gene expression changes were evident between 6 and 24 hours after infection, which was influenced by the infected cell type; however, virulence genes were not significantly altered. While infection of the airway epithelium induced rapid and dynamic inflammatory signalling, the alveolar epithelium demonstrated augmented cell death and mounted a transcriptional pro-inflammatory and proliferative response that was uncoupled from cytokine secretion. The airway epithelium model exhibited consistently higher baseline type I interferon (IFN) signalling than the alveolar epithelium. Invasion by S. pyogenes and inflammation was significantly reduced in IFN-{beta}-treated alveolar epithelial cells. In summary, we have established the first model of S. pyogenes infection in physiologically relevant airway and alveolar epithelial cells. Our findings suggest that host responses to infection are influenced by lung compartment, the S. pyogenes strain type, and infection timepoint, highlighting context-specific pathways that could be leveraged therapeutically.

microbiology↗

bioRxiv2025

The synovial lining macrophage layer develops in the first weeks of life in a CSF1- and TGFβ- dependent but monocyte-independent process.

Synovial joints harbor a protective lining layer, consisting of fibroblasts and macrophages, which form an epithelial-like barrier. In inflamed joints, lining macrophages regulate both early inflammatory cell influx and resolution. Despite these critical functions, it is currently unknown at what stage during development the synovial macrophage lining is established, and which signals drive this process. Here, we use a combination of genetic models and in vivo perturbations, single cell transcriptomics and imaging to delineate the process of lining formation in mice. We find that the synovial lining is immature at birth and becomes established within the first 3 weeks of life. In this window, the lining is gradually populated with macrophages that originate from fetal sources, proliferate and acquire the lining-specific transcriptional identity. In contrast, monocytes contribute only minimally to the developing lining, and their input remains limited in healthy adulthood. We identify CSF1 and TGF{beta} as key signals in this process, which also involves mechanosensing through PIEZO1. Our study thus identifies the early postnatal window as a critical period for lining macrophage development, with potential lifelong impact on joint health and disease.

immunology↗

bioRxiv2025

Macrophages Mediate Antiviral Immunity and Repair of Type 2 Alveolar Epithelial Cells in a Human Stem Cell Model

The lung alveoli are constantly exposed to inhaled pathogens and inorganic hazards, relying on robust defence mechanisms to maintain homeostasis. Alveolar macrophages and type 2 alveolar epithelial cells (AT2s) collaborate to orchestrate protection. Compromised defence can dysregulate immunity and repair, leading to acute and chronic respiratory diseases. To better understand these processes and drive therapeutic discovery, human model systems that capture key cell interactions are essential. Here, we develop the first induced pluripotent stem cell (iPSC)-derived platform that integrates AT2 cells and macrophages in an air-liquid interface culture. Coculture enhanced AT2-specific gene expression and lipid synthesis, while macrophages actively phagocytosed AT2-derived surfactant. iPSC-derived AT2s supported macrophage survival by producing M-CSF and coculture promoted an alveolar macrophage-like phenotype. Additionally, during respiratory infection macrophages played a crucial role in modulating proinflammatory signalling, enhancing antiviral immunity, and restricting viral replication. Furthermore, we identify a role for iPSC-derived macrophages in epithelial repair, with VEGF signalling to macrophages increasing epithelial permeability. We present an iPSC-derived air-interface platform to study AT2-macrophage interactions in homeostasis, infection, and repair, providing insights into their potential roles in the initiation and progression of respiratory diseases.

cell biology↗

bioRxiv2024

Mast cells are not essential for pubertal mammary gland branching.

Mast cells are long-lived, tissue-resident immune cells of the myeloid lineage with cardinal functions in allergy and atopic disease. They are now increasingly recognized also for protective roles e.g. against infections and venoms. Other functions originally assigned to mast cells in development and physiology, however, have been refuted, and for yet others, their true contribution remains uncertain. Mast cells have been implicated in promoting ductal branching in the pubertal mammary gland, the organ that produces and secretes milk in mammals, but these findings are based on mouse models that are not mast cell-specific. In this study, we therefore re-addressed the impact of mast cells on mammary gland branching using several complementary genetic models, including a new transgenic line. We report that neither constitutive deficiency of mast cells, nor their conditional ablation induced at puberty affected mammary gland branching. Our results thus dispute that mast cells promote this process in mice, at least in a unique and non-redundant manner. This study adds to a growing body of work clarifying the biological roles of mast cells, and further expands the toolbox available to the field of mast cell research.

developmental biology↗