Biology subjects

Spann, K. M.

Publications and source records attributed to Spann, K. M..

3 recordsLinked to original sources

bioRxiv2026

Dissecting Immune-Epithelial Interactions in Airway Infection at Single-Cell Resolution Using a Compartmentalised Microfluidic Device

Immune-epithelial interactions govern the initiation and progression of airway diseases, yet their heterogeneity is difficult to capture using existing in vitro models. Although conventional Transwell and lung-on-chip systems reproduce airway compartmentalisation and permit epithelial-immune interactions, they lack the spatial and analytical resolution needed to visualise dynamic immune behaviour during infection. Here, we present the "Single Cell resolved Airway-Immune Recruitment" (scAIR) platform designed to interrogate immune-epithelial interactions during airway infection. The scAIR device features a modular central chamber accommodating a Transwell insert with primary airway epithelial cells (AECs) pre-differentiated under air-liquid interface (ALI), flanked by immune compartments connected through a precision-patterned microchannel array. This architecture enables real-time single-cell imaging of immune cell migration while preserving epithelial physiology. The scAIR device coupled with a machine learning analysis (MLA) pipeline enables automated tracking and quantification of individual immune cell speed, direction, and behavioural heterogeneity. Using this platform, respiratory syncytial virus (RSV) infection is modelled to generate a type 1 inflammatory airway epithelium that drives neutrophil recruitment. TNF-alpha neutralisation with adalimumab reveals distinct migratory behaviours that are obscured by population-averaged measurements. This integrated platform quantifies airway immune responses during infection and therapeutic modulation, enabling mechanistic studies, drug evaluation, and precision modelling of airway inflammation.

bioengineering↗

bioRxiv2024

A maternal high-fat diet predisposes to infant lung disease via increased neutrophil-mediated IL-6 trans-signaling

Poor maternal diet during pregnancy predisposes to severe lower respiratory tract infections (sLRI) in infancy, which in turn, increases childhood asthma risk, however the underlying mechanisms remain poorly understood. Here, we show that the offspring of high fat diet (HFD)-fed mothers ( HFD-reared pups) developed a sLRI following pneumovirus inoculation in early-life and subsequent asthma in later-life upon allergen exposure. Prior to infection, HFD-reared pups developed microbial dysbiosis and low-grade systemic inflammation (LGSI), characterized by hyper-granulopoiesis in the liver and elevated inflammatory cytokine expression, most notably IL-17A, IL-6 and sIL-6R (indicative of IL-6 trans-signaling) in the circulation and multiple organs, but most prominently the liver. Inhibition of IL-6 trans-signaling, using sgp130Fc transgenic mice or via specific genetic deletion of IL-6Ra on neutrophils, conferred protection against both diseases. Taken together, our findings suggest that a maternal HFD induces neonatal LGSI that predisposes to sLRI and subsequent asthma via neutrophil-mediated IL-6 trans-signaling.

immunology↗

bioRxiv2021

Pediatric nasal epithelial cells are less permissive to SARS-CoV-2 replication compared to adult cells

Children typically experience more mild symptoms of COVID-19 when compared to adults. There is a strong body of evidence that children are also less susceptible to SARS-CoV-2 infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remains to be determined. Here, we use primary nasal epithelial cells from children and adults, differentiated at an air-liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the nasal epithelial cells of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the nasal epithelial cells of children. Importantly, the Delta variant also replicated to significantly lower titres in the nasal epithelial cells of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves.

microbiology↗