Deborah Strickland
Program Head, Immunobiology and Immunotherapeutic Program
PhD
deb.strickland@telethonkids.org.au
Associate Prof Strickland completed her PhD at the University of WA in the regulation of immune homeostatic processes in the respiratory tract. She received a prestigious Elizabeth Albeiz Fellowship (Multiple Sclerosis Society of Australia) for post-doctoral studies at the Centenary Institute, Sydney.
Following this, her postdoctoral work focused on establishing an independent program of research to explore the pathogenic mechanisms associated with risk for allergic asthma inception and progression, particularly during early life. In parallel, she has established a complimentary research program to explore how inflammatory responses that occur in the mother during gestation can perturb the developing fetal immune system to result in increased risk for a range of diseases (including respiratory, metabolic, and neurological systems) in later life.
Her research program is targeted towards addressing key fundamental gaps in the understanding of immune development, homeostatic mechanisms and how the immune system can be programmed to drive increased disease susceptibility, or trained to mitigate disease risk, with the overarching goal of developing potential preventive strategies. Her current positions are as Team Leader Experimental Immunology, Athena Swan Chair, Early Environment Research Focus Area chair, Adjunct Assoc Prof UWA.
Projects
ORIGINS of Neurodevelopmental Risk and Resilience
This project aims to better understand the early genetic and environmental factors that the developing brain during a child’s first five years of life.
Mechanisms of Acute Viral Respiratory Illness in Children (MAVRIC)
Precision pathways for young children at risk of Neurodevelopmental Disorders: Early identification and adaptive intervention starting from the prenatal period
Using Systems Biology to understand asthma exacerbations and develop better treatments
Understanding how viral infection in early life impacts on lung function in adulthood
An immunometabolomic approach to unmask developmental regulation of innate immunity and asthma risk
Acute viral bronchiolitis in infants and young children
Evaluation of a bacterial therapy for prevention of respiratory infection including influenza and otitis media
Asthma: Acute asthma flare-up in school-age children
The aim of this study is to identify differences in immune cells that are involved in the disease.
Acute viral bronchiolitis in infants and young children
This project aims to plug this knowledge gap, and to open up new opportunities for development of better treatments targeted specifically at infants.
Attenuation of maternal inflammatory responses during pregnancy to promote normal immune and behavioral outcomes in the offspring
This study will identify how the immune system contributes to neurodevelopmental outcomes and will investigate the use of an agent from traditional medicines.
The impact of Influenza infection during early life on immune development
This study will investigate the why disease is worse in infants and how early life viral infection impacts the developing immune system.
Mapping changes in immune cell populations in gestational tissues over the course of pregnancy
This is a strategic “pilot” project in which we are seeking basic information on the immune cell content of gestational tissues.
Long-term derangement of antigen presenting cell populations in the respiratory tract following Influenza A infection
This project investigates how different populations of cells within the respiratory tract immune system are altered during a viral infection.
Finding the cellular explanation for recurrent asthma exacerbations
This study is designed to identify the specific unique immune cell response that occurs in these children with recurrent disease.
Targeting the mucosal immune system in a pregnant mouse model to prevent experimental allergic airways disease in the offspring
Studies in Europe show exposure of pregnant women to high levels of microbial products stimulate immune function maturation in their offspring
The cellular effects of estrogen on allergic asthma
The study aims to identify the mechanism for this so that this knowledge can be used to better treat asthma and allergies in both males and females.
Mechanisms of IgE sensitization
This project investigates how cells of the immune system respond to substances to cause allergies to help develop new treatments.
October 2016
Targeting the mucosal immune system in a mouse model to prevent pregnancy complications following maternal bacterial infection
This work is the first step to develop safe treatments for pregnant mums to protect against preterm delivery and low birth weight caused by maternal infections.
Studies on the immunological mechanisms underlying progression versus resolution of asthma between adolescence and adulthood
This project seeks new information on asthma disease mechanisms, to help propel development of new and better anti-asthma drugs.
Epigenetic changes underpinning allergen sensitization: a twin-based study
We are studying immune cells from identical twins of which one suffers and one does not suffer from allergic disease to identify specific mechanisms that may pl
Published research
Nasal Delivery of Haemophilus haemolyticus Is Safe, Reduces Influenza Severity, and Prevents Development of Otitis Media in Mice
Despite vaccination, influenza and otitis media (OM) remain leading causes of illness. We previously found that the human respiratory commensal Haemophilus haemolyticus prevents bacterial infection in vitro and that the related murine commensal Muribacter muris delays OM development in mice. The observation that M muris pretreatment reduced lung influenza titer and inflammation suggests that these bacteria could be exploited for protection against influenza/OM.
An infant mouse model of influenza-driven nontypeable Haemophilus influenzae colonization and acute otitis media suitable for preclinical testing of novel therapies
Nontypeable Haemophilus influenzae (NTHi) is a major otitis media (OM) pathogen, with colonization a prerequisite for disease development. Most acute OM is in children <5 years old, with recurrent and chronic OM impacting hearing and learning. Therapies to prevent NTHi colonization and/or disease are needed, especially for young children. Respiratory viruses are implicated in driving the development of bacterial OM in children.
Mapping Lung Hematopoietic Progenitors: Developmental Kinetics and Response to Influenza A Infection
The bone marrow is a specialised niche responsible for the maintenance of hematopoietic stem and progenitor cells during homeostasis and inflammation. Recent studies however have extended this essential role to the extramedullary and extravascular lung microenvironment. Here, we provide further evidence for a reservoir of hematopoietic stem and progenitor cells within the lung from embryonic day 18.5 until adulthood.
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.
September 2011
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).