Deborah Strickland

Impaired interferon response in plasmacytoid dendritic cells from children with persistent wheeze

Impaired interferon response and allergic sensitization may contribute to virus-induced wheeze and asthma development in young children. Plasmacytoid dendritic cells play a key role in antiviral immunity as critical producers of type I interferons. 

Egg-sensitised infants have elevated CD4+ effector memory T regulatory cells from birth

IgE-mediated sensitisation to egg is common in infants. In some cases, the processes leading to egg sensitisation are established in early life, even before introduction to solid foods. The underlying mechanisms remain poorly understood. 

Single cell transcriptomics reveals cell type specific features of developmentally regulated responses to lipopolysaccharide between birth and 5 years

Human perinatal life is characterized by a period of extraordinary change during which newborns encounter abundant environmental stimuli and exposure to potential pathogens. To meet such challenges, the neonatal immune system is equipped with unique functional characteristics that adapt to changing conditions as development progresses across the early years of life, but the molecular characteristics of such adaptations remain poorly understood.

In Vivo Evidence of Respiratory Syncytial Virus Persistence in a Subset of Pulmonary Dendritic Cells Following a Primary Infection

Respiratory syncytial virus (RSV) causes annual epidemics of infections affecting the whole population. In vitro, it has been shown to infect and persist in human dendritic cells (DCs) for prolonged periods. Initially persistence is associated with low levels of replication before the virus becomes dormant. Reactivation of viral replication can be triggered many months later.

LPS binding protein and activation signatures are upregulated during asthma exacerbations in children

Asthma exacerbations in children are associated with respiratory viral infection and atopy, resulting in systemic immune activation and infiltration of immune cells into the airways. The gene networks driving the immune activation and subsequent migration of immune cells into the airways remains incompletely understood. Cellular and molecular profiling of PBMC was employed on paired samples obtained from atopic asthmatic children during acute virus-associated exacerbations and later during convalescence.

Associations between the human immune system and gut microbiome with neurodevelopment in the first 5 years of life: A systematic scoping review

The aim of this review was to map the literature assessing associations between maternal or infant immune or gut microbiome biomarkers and child neurodevelopmental outcomes within the first 5 years of life. We conducted a PRISMA-ScR compliant review of peer-reviewed, English-language journal articles.

Potential immunological effects of gender-affirming hormone therapy in transgender people – an unexplored area of research

There are well-described sex-based differences in how the immune system operates. In particular, cisgender (cis) females have a more easily activated immune system; associated with an increased prevalence of autoimmune diseases and adverse events following vaccinations. Conversely, cis males have a higher threshold for immune activation, and are more prone to certain infectious diseases, such as coronavirus disease (COVID-19).

Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life

Appropriate innate immune function is essential to limit pathogenesis and severity of severe lower respiratory infections (sLRI) during infancy, a leading cause of hospitalization and risk factor for subsequent asthma in this age group.

Protection against severe infant lower respiratory tract infections by immune training: Mechanistic studies

Results from recent clinical studies suggest potential efficacy of immune training (IT)-based approaches for protection against severe lower respiratory tract infections in infants, but underlying mechanisms are unclear.

Exacerbation of chronic cigarette-smoke induced lung disease by rhinovirus in mice

A significant proportion of chronic obstructive pulmonary disease exacerbations are strongly associated with rhinovirus infection (HRV). In this study, we combined long-term cigarette smoke exposure with HRV infection in a mouse model.

Innate Immune Training for Prevention of Recurrent Wheeze in Early Childhood

IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming

High risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high versus low susceptibility to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype.

Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM-85

Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial-derived immune training agent OM-85 during pregnancy promotes accelerated postnatal maturation of mechanisms that regulate inflammatory processes in the offspring airways.

Prebiotic Supplementation During Pregnancy Modifies the Gut Microbiota and Increases Metabolites in Amniotic Fluid, Driving a Tolerogenic Environment In Utero

The gut microbiota is influenced by environmental factors such as food. Maternal diet during pregnancy modifies the gut microbiota composition and function, leading to the production of specific compounds that are transferred to the fetus and enhance the ontogeny and maturation of the immune system. Prebiotics are fermented by gut bacteria, leading to the release of short-chain fatty acids that can specifically interact with the immune system, inducing a switch toward tolerogenic populations and therefore conferring health benefits.

Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM-85

Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial-derived immune training agent OM-85 during pregnancy promotes accelerated postnatal maturation of mechanisms that regulate inflammatory processes in the offspring airways.

OMIP 076: High-dimensional immunophenotyping of murine T-cell, B-cell, and antibody secreting cell subsets

There is now considerable evidence demonstrating that both prenatal and postnatal exposure to particular classes of microbial stimuli can provide beneficial signals during early life immune development, resulting in the protection against future inflammatory disease.

Metabolic dysfunction induced by a high-fat diet modulates hematopoietic stem and myeloid progenitor cells in brown adipose tissue of mice

Brown adipose tissue (BAT) may be an important metabolic regulator of whole-body glucose. While important roles have been ascribed to macrophages in regulating metabolic functions in BAT, little is known of the roles of other immune cells subsets, particularly dendritic cells (DCs). Eating a high-fat diet may compromise the development of hematopoietic stem and progenitor cells (HSPCs)-which give rise to DCs-in bone marrow, with less known of its effects in BAT. We have previously demonstrated that ongoing exposure to low-dose ultraviolet radiation (UVR) significantly reduced the 'whitening' effect of eating a high-fat diet upon interscapular (i) BAT of mice.

Transplacental Innate Immune Training via Maternal Microbial Exposure: Role of XBP1-ERN1 Axis in Dendritic Cell Precursor Programming

We recently reported that offspring of mice treated during pregnancy with the microbial-derived immunomodulator OM-85 manifest striking resistance to allergic airways inflammation, and localized the potential treatment target to fetal conventional dendritic cell (cDC) progenitors. Here, we profile maternal OM-85 treatment-associated transcriptomic signatures in fetal bone marrow, and identify a series of immunometabolic pathways which provide essential metabolites for accelerated myelopoiesis.

Nasal delivery of a commensal Pasteurellaceae species inhibits nontypeable Haemophilus influenzae colonisation and delays onset of otitis media in mice

We have demonstrated that a single dose of a closely related commensal can delay onset of NTHi otitis media in vivo

Oestrogen amplifies pre-existing atopy-associated Th2 bias in an experimental asthma model

The role of oestrogen in experimental atopic asthma, and guide future research on sex-related variations in atopic asthma susceptibility/intensity

A method for the generation of large numbers of dendritic cells from CD34+ hematopoietic stem cells from cord blood

Neonatal dendritic cells generated form CD34+ cord blood progenitors have a higher inflammatory potential when exposed to viral than bacterial related stimuli

Immunoinflammatory responses to febrile lower respiratory infections in infants display uniquely complex/intense transcriptomic profiles

the association between infant LRTI and risk for persistent wheeze/asthma in this cohort is generally stronger for fLRTIs than for other infection categories

Progressive increase of FcεRI expression across several PBMC subsets is associated with atopy and atopic asthma within school-aged children

The expression pattern of FcεRI on DC and basophils differentiates asthmatic from non-asthmatic atopic children

Personalized transcriptomics reveals heterogeneous immunophenotypes in children with viral bronchiolitis

Dysregulated expression of IFN-dependent pathways after respiratory viral infections is a defining immunophenotypic feature of AVB-susceptible infants

Pregnancy Induces a Steady-State Shift in Alveolar Macrophage M1/M2 Phenotype That Is Associated With a Heightened Severity of Influenza Virus Infection

Pregnancy is associated with an alternatively activated phenotype of alveolar macrophage before infection

Quantification of Serum Ovalbumin-specific Immunoglobulin E Titre via in vivo Passive Cutaneous Anaphylaxis Assay

We describe herein a highly reproducible in vivo passive cutaneous anaphylaxis assay using Sprague Dawley rats for the quantification of ovalbumin-specific IgE

Early Life Ovalbumin Sensitization and Aerosol Challenge for the Induction of Allergic Airway Inflammation in a BALB/c Murine Model

This protocol adapted an experimental animal model of disease for sensitization to ovalbumin during the immediate post-weaning period beginning at 21 days of age

Transplacental immune modulation with a bacterial-derived agent protects against allergic airway inflammation

These data provide proof of concept supporting the rationale for developing transplacental immune reprogramming approaches for primary disease prevention

Basophil counts in PBMC populations during childhood acute wheeze/asthma are associated with future exacerbations

Our findings suggest that the proportion of degranulated basophils can also be associated with recurrent exacerbations

Atopy-dependent and independent immune responses in the heightened severity of atopics to respiratory viral infections: Rat model studies

The co-exposure responses in the Th2high BN incorporated type I interferon/Th1, alternative macrophage activation/Th2 and Th17 signatures

Immunological processes driving IgE sensitisation and disease development in males and females

In this review, we discuss recent mechanistic studies casting further light on how the expression of sex hormones may influence the innate and adaptive immune system

Functional differences in airway dendritic cells determine susceptibility to IgE-sensitization

Respiratory IgE-sensitization to innocuous antigens increases the risk for developing diseases such as allergic asthma.

Protection against maternal infection-associated fetal growth restriction: Proof-of-concept with a microbial-derived immunomodulator

This study suggests that broad-spectrum protection-of-pregnancy against infection-associated inflammatory stress represents an achievable therapeutic goal

Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea

We aimed to explore whether newborns in high-risk areas have pre-existing pneumococcal-specific cellular immune responses that effects early acquisition.

A pathogenic role for the integrin CD103 in experimental allergic airways disease

Role for CD103 in the pathogenesis of experimental allergic airways disease in BALB/c mice through local control of CD4+ T cell and DC subset recruitment

Distinguishing benign from pathologic TH2 immunity in atopic children

In addition to its role in blocking TH2 effector activation in the late-phase allergic response, IL-10 is a known IgG1 switch factor

Persistent and compartmentalised disruption of dendritic cell subpopulations in the lung following influenza A virus infection

Immunological homeostasis in the respiratory tract is thought to require balanced interactions between networks of dendritic cell (DC) subsets in lung...

Genome-wide DNA methylation profiling identifies a folate-sensitive region of differential methylation upstream of ZFP57-imprinting regulator in humans

This study identified that expsoure to folate has effects on the regulation of DNA methylation during fetal development.

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell...

Defective respiratory tract immune surveillance in asthma : A primary causal factor in disease onset and progression

The relative importance of respiratory viral infections vs inhalant allergy in asthma pathogenesis is the subject of ongoing debate.

Size-Dependent Uptake of Particles by Pulmonary Antigen-Presenting Cell Populations

The respiratory tract is an attractive target organ for novel diagnostic and therapeutic applications with nano-sized carriers, but their immune effects and...

Altered immunity and dendritic cell activity in the periphery of mice after long-term engraftment with bone marrow from ultraviolet-irradiated mice

To investigate the immune capabilities of peripheral tissue DCs generated in vivo from the BM of UV-irradiated mice, chimeric mice were established.

Neonatal antigen-presenting cells are functionally more quiescent in children born under traditional compared with modern environmental conditions

One explanation for the high burden of allergic and autoimmune diseases in industrialized countries is inappropriate immune development under modern...

Toward homeostasis: Regulatory dendritic cells from the bone marrow of mice with inflammation

Inflammatory mediators from peripheral tissues may control dendritic cell (DC) development in the bone marrow.

Ontogeny of toll-like and NOD-like receptor-mediated innate immune responses in Papua New Guinean infants

Studies addressing the ontogeny of the innate immune system in early life have reported mainly on Toll-like receptor (TLR) responses in infants living in...

Defective aeroallergen surveillance by airway mucosal dendritic cells as a determinant of risk

A hallmark of atopic asthma is development of chronic airways hyper-responsiveness (AHR) that persists in the face of ongoing exposure to perennial...

Virus infection and allergy in the development of asthma: What is the connection?

Information is accumulating which implicates airway inflammation resulting from respiratory viral infections, acting against a background of atopy.

Comparison of neonatal T regulatory cell function in Papua New Guinean and Australian newborns

We compared neonatal T reg from children born in western conditions (Australia) with those of neonates born in high microbial conditions (Papua New Guinea)...

Inert 50-nm Polystyrene Nanoparticles That Modify Pulmonary Dendritic Cell Function and Inhibit Allergic Airway Inflammation

Nanoparticles are being developed for diverse biomedical applications, but there is concern about potential to promote inflammation, particularly in the lungs.

T regulatory cells in childhood asthma

Asthma is a chronic disease of the airways, most commonly driven by immuno-inflammatory responses to ubiquitous airborne antigens.

Restricted aeroallergen access to airway mucosal dendritic cells in vivo limits allergen-specific

Chronic innocuous aeroallergen exposure attenuates CD4+ T cell-mediated airways hyperresponsiveness in mice; however, the mechanism(s) remain unclear

Boosting airway T-regulatory cells by gastrointestinal stimulation as a strategy for asthma control

The hallmark of atopic asthma is transient airways hyperresponsiveness (AHR) preceded by aeroallergen-induced Th-cell activation.

Epithelial-dendritic cell interactions in allergic disorders

Airway epithelial cells act through multiple mechanisms to function as an important component of the pulmonary defence strategy that is crucial...

Interactions between innate and adaptive immunity in asthma pathogenesis: new perspectives from studies on acute exacerbations

Atopic asthma, which is at its highest prevalence during childhood/young adulthood, represents the main focus of this review.

UV exposure and protection against allergic airways disease

Asthma is a chronic inflammatory disease of the small and large conducting airway mucosa characterised by Th2 cell immunity.

The role of dendritic cells and regulatory T cells in the regulation of allergic asthma

Airways hyperresponsiveness (AHR) is one of the major clinical features of allergic airways disease including allergic asthma

Identification and Isolation of Rodent Respiratory Tract Dendritic Cells

This chapter describes the preparation of respiratory tract tissue from both mice and rats for the isolation of respiratory tract dendritic cells (RTDC).