Publications by year
In Press
Drummond RA, Swamydas M, Oikonomou V, Zhai B, Dambuza I, Schaefer BC, Bohrer AC, Mayer-Barber KD, Lira SA, Iwakura Y, et al (In Press). CARD9+ microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment.
Nature Immunology,
20, 559-570.
Abstract:
CARD9+ microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment
The C-type lectin receptor/Syk adaptor CARD9 facilitates protective antifungal immunity within the central nervous system (CNS), as human CARD9-deficiency causes fungal-specific CNS-targeted infection susceptibility. We previously showed that CARD9 is required for neutrophil recruitment to the fungal-infected CNS, which mediates fungal clearance. Here, we investigated host and pathogen factors that promote protective neutrophil recruitment during Candida albicans CNS invasion and examined their dependence on CARD9 for in vivo induction. We show that IL-1b is essential for CNS antifungal immunity by driving CXCL1 production, which recruits CXCR2-expressing neutrophils. Neutrophil-recruiting IL-1b and CXCL1 production is induced in microglia by the fungal-secreted peptide toxin Candidalysin, in a p38-cFos-dependent manner. Importantly, microglia rely on CARD9 for production of IL-1b, via both pro-IL-1b transcriptional regulation and inflammasome activation, and of CXCL1 in the fungal-infected CNS, and we show that microglia-specific CARD9 deletion impairs IL40 1b and CXCL1 production and neutrophil recruitment, and increases CNS fungal proliferation. Our data reveals an intricate network of host-pathogen interactions that promotes CNS antifungal immunity and provides novel mechanistic insights into how human CARD9-deficiency causes CNS fungal disease.
Abstract.
Drummond RA, Dambuza IM, Vautier S, Taylor JA, Reid DM, Bain CC, Underhill DM, Masopust D, Kaplan DH, Brown GD, et al (In Press). CD4+ T-cell survival in the GI tract requires dectin-1 during fungal infection.
Mucosal Immunology,
9, 492-502.
Abstract:
CD4+ T-cell survival in the GI tract requires dectin-1 during fungal infection
Dectin-1 is an innate antifungal C-type lectin receptor necessary for protective antifungal immunity. We recently discovered that Dectin-1 is involved in controlling fungal infections of the gastrointestinal (GI) tract, but how this C-type lectin receptor mediates these activities is unknown. Here, we show that Dectin-1 is essential for driving fungal-specific CD4+ T-cell responses in the GI tract. Loss of Dectin-1 resulted in abrogated dendritic cell responses in the mesenteric lymph nodes (mLNs) and defective T-cell co-stimulation, causing substantial increases in CD4+ T-cell apoptosis and reductions in the cellularity of GI-associated lymphoid tissues. CD8+ T-cell responses were unaffected by Dectin-1 deficiency. These functions of Dectin-1 have significant implications for our understanding of intestinal immunity and susceptibility to fungal infections.
Abstract.
Dambuza IM, Levitz SM, Netea MG, Brown GD (In Press). Fungal Recognition and Host Defense Mechanisms.
Microbiology spectrum,
5, 1-16.
Abstract:
Fungal Recognition and Host Defense Mechanisms
Fungi have emerged as premier opportunistic microbes of the 21st century, having a considerable impact on human morbidity and mortality. The huge increase in incidence of these diseases is largely due to the HIV pandemic and use of immunosuppressive therapies, underscoring the importance of the immune system in defense against fungi. This article will address how the mammalian immune system recognizes and mounts a defense against medically relevant fungal species.
Abstract.
Dambuza IM, Wagener J, Brown GD, Gow NAR (In Press). Immunology of fungal disease. In Kibbler CC, Barton R, Gow NAR, Howell S, MacCallum DM, Manuel RJ (Eds.)
Oxford Textbook of Medical Mycology, Oxford University Press.
Abstract:
Immunology of fungal disease
Abstract.
Dambuza IM, Brown GD (In Press). Sensing fungi at the oral epithelium.
Nature Microbiology,
3, 4-5.
Abstract:
Sensing fungi at the oral epithelium
The mechanisms involved in controlling Candida albicans at mucosal sites are not fully understood. Recent work identifies the EphA2 on epithelial cells as a fungal β-glucan receptor that is critical for mediating protective immunity during oral candidiasis.
Abstract.
Dambuza IM, Drake T, Chapuis A, Zhou X, Correia J, Taylor-Smith L, Legrave N, Rasmussen T, Fisher MC, Bicanic T, et al (In Press). The Cryptococcus neoformans Titan cell is an inducible and regulated morphotype underlying pathogenesis.
PLoS Pathogens,
14, 1-28.
Abstract:
The Cryptococcus neoformans Titan cell is an inducible and regulated morphotype underlying pathogenesis
Fungal cells change shape in response to environmental stimuli, and these morphogenic transitions drive pathogenesis and niche adaptation. For example, dimorphic fungi switch between yeast and hyphae in response to changing temperature. The basidiomycete Cryptococcus neoformans undergoes an unusual morphogenetic transition in the host lung from haploid yeast to large, highly polyploid cells termed Titan cells. Titan cells influence fungal interaction with host cells, including through increased drug resistance, altered cell size, and altered Pathogen Associated Molecular Pattern exposure. Despite the important role these cells play in pathogenesis, understanding the environmental stimuli that drive the morphological transition, and the molecular mechanisms underlying their unique biology, has been hampered by the lack of a reproducible in vitro induction system. Here we demonstrate reproducible in vitro Titan cell induction in response to environmental stimuli consistent with the host lung. In vitro Titan cells exhibit all the properties of in vivo generated Titan cells, the current gold standard, including altered capsule, cell wall, size, high mother cell ploidy, and aneuploid progeny. We identify the bacterial peptidoglycan subunit Muramyl Dipeptide as a serum compound associated with shift in cell size and ploidy, and demonstrate the capacity of bronchial lavage fluid and bacterial co-culture to induce Titanisation. Additionally, we demonstrate the capacity of our assay to identify established (cAMP/PKA) and previously undescribed (USV101) regulators of Titanisation in vitro. Finally, we investigate the Titanisation capacity of clinical isolates and their impact on disease outcome. Together, these findings provide new insight into the environmental stimuli and molecular mechanisms underlying the yeast-to-Titan transition and establish an essential in vitro model for the future characterization of this important morphotype.
Abstract.
2022
Nicola AM, Desai JV, Swidergall M, Shey M, Dambuza IM (2022). Editorial: Immunological Memory to Fungal Infections and Vaccine Development.
FRONTIERS IN IMMUNOLOGY,
13 Author URL.
Avelar GM, Dambuza IM, Ricci L, Yuecel R, Mackenzie K, Childers DS, Bain JM, Pradhan A, Larcombe DE, Netea MG, et al (2022). Impact of Changes at the Candida Albicans Cell Surface Upon Immunogenicity and Colonisation in the Gastrointestinal Tract.
Avelar GM, Dambuza IM, Ricci L, Yuecel R, Mackenzie K, Childers DS, Bain JM, Pradhan A, Larcombe DE, Netea MG, et al (2022). Impact of changes at the Candida albicans cell surface upon immunogenicity and colonisation in the gastrointestinal tract.
Cell Surf,
8Abstract:
Impact of changes at the Candida albicans cell surface upon immunogenicity and colonisation in the gastrointestinal tract.
The immunogenicity of Candida albicans cells is influenced by changes in the exposure of microbe-associated molecular patterns (MAMPs) on the fungal cell surface. Previously, the degree of exposure on the C. albicans cell surface of the immunoinflammatory MAMP β-(1,3)-glucan was shown to correlate inversely with colonisation levels in the gastrointestinal (GI) tract. This is important because life-threatening systemic candidiasis in critically ill patients often arises from translocation of C. albicans strains present in the patient's GI tract. Therefore, using a murine model, we have examined the impact of gut-related factors upon β-glucan exposure and colonisation levels in the GI tract. The degree of β-glucan exposure was examined by imaging flow cytometry of C. albicans cells taken directly from GI compartments, and compared with colonisation levels. Fungal β-glucan exposure was lower in the cecum than the small intestine, and fungal burdens were correspondingly higher in the cecum. This inverse correlation did not hold for the large intestine. The gut fermentation acid, lactate, triggers β-glucan masking in vitro, leading to attenuated anti-Candida immune responses. Additional fermentation acids are present in the GI tract, including acetate, propionate, and butyrate. We show that these acids also influence β-glucan exposure on C. albicans cells in vitro and, like lactate, they influence β-glucan exposure via Gpr1/Gpa2-mediated signalling. Significantly, C. albicans gpr1Δ gpa2Δ cells displayed elevated β-glucan exposure in the large intestine and a corresponding decrease in fungal burden, consistent with the idea that Gpr1/Gpa2-mediated β-glucan masking influences colonisation of this GI compartment. Finally, extracts from the murine gut and culture supernatants from the mannan grazing gut anaerobe Bacteroides thetaiotaomicron promote β-glucan exposure at the C. albicans cell surface. Therefore, the local microbiota influences β-glucan exposure levels directly (via mannan grazing) and indirectly (via fermentation acids), whilst β-glucan masking appears to promote C. albicans colonisation of the murine large intestine.
Abstract.
Author URL.
Pradhan A, Ma Q, Hickey E, Avelar G, Larcombe D, Bain J, Childers D, Dambuza I, Leaves I, de Assis LJ, et al (2022). S9.4c Diverse environmental inputs mediate changes in β-glucan exposure at the Candida albicans cell surface thereby influencing tissue colonisation during systemic infection. Medical Mycology, 60(Suppl 1).
2021
Zhou X, Desanti GE, May RC, Dambuza IM, Ballou ER (2021). Host-derived Reactive Nitrogen Species mediate the Cryptococcus neoformans yeast-to-titan switch via fungal-derived superoxide.
Dambuza IM, Brown GD (2021). Managing the mycobiota with IgA.
Nat Microbiol,
6(12), 1471-1472.
Author URL.
Tone K, Stappers MHT, Hatinguais R, Dambuza IM, Salazar F, Wallace C, Yuecel R, Morvay PL, Kuwano K, Willment JA, et al (2021). MelLec Exacerbates the Pathogenesis of Aspergillus fumigatus-Induced Allergic Inflammation in Mice.
Frontiers in Immunology,
12Abstract:
MelLec Exacerbates the Pathogenesis of Aspergillus fumigatus-Induced Allergic Inflammation in Mice
Environmental factors, particularly fungi, influence the pathogenesis of allergic airway inflammation, but the mechanisms underlying these effects are still unclear. Melanin is one fungal component which is thought to modulate pulmonary inflammation. We recently identified a novel C-type lectin receptor, MelLec (Clec1a), which recognizes fungal 1,8-dihydroxynaphthalene (DHN)-melanin and is able to regulate inflammatory responses. Here we show that MelLec promotes pulmonary allergic inflammation and drives the development of Th17 T-cells in response to spores of Aspergillus fumigatus. Unexpectedly, we found that MelLec deficiency was protective, with MelLec-/- animals showing normal weight gain and significantly reduced pulmonary inflammation in our allergic model. The lungs of treated MelLec-/- mice displayed significantly reduced inflammatory foci and reduced bronchial wall thickening, which correlated with a reduced cellular influx (particularly neutrophils and inflammatory monocytes) and levels of inflammatory cytokines and chemokines. Notably, fungal burdens were increased in MelLec-/- animals, without apparent adverse effects, and there were no alterations in the survival of these mice. Characterization of the pulmonary T-cell populations, revealed a significant reduction in Th17 cells, and no alterations in Th2, Th1 or Treg cells. Thus, our data reveal that while MelLec is required to control pulmonary fungal burden, the inflammatory responses mediated by this receptor negatively impact the animal welfare in this allergic model.
Abstract.
Baldassarre M, Solano-Collado V, Balci A, Colamarino RA, Dambuza IM, Reid DM, Wilson HM, Brown GD, Mukhopadhyay S, Dougan G, et al (2021). The Rab32/BLOC-3-dependent pathway mediates host defense against different pathogens in human macrophages.
Science Advances,
7(3).
Abstract:
The Rab32/BLOC-3-dependent pathway mediates host defense against different pathogens in human macrophages
Macrophages provide a first line of defense against microorganisms, and while some mechanisms to kill pathogens such as the oxidative burst are well described, others are still undefined or unknown. Here, we report that the Rab32 guanosine triphosphatase and its guanine nucleotide exchange factor BLOC-3 (biogenesis of lysosome-related organelles complex-3) are central components of a trafficking pathway that controls both bacterial and fungal intracellular pathogens. This host-defense mechanism is active in both human and murine macrophages and is independent of well-known antimicrobial mechanisms such as the NADPH (reduced form of nicotinamide adenine dinucleotide phosphate)-dependent oxidative burst, production of nitric oxide, and antimicrobial peptides. To survive in human macrophages, Salmonella Typhi actively counteracts the Rab32/BLOC-3 pathway through its Salmonella pathogenicity island-1-encoded type III secretion system. These findings demonstrate that the Rab32/BLOC-3 pathway is a novel and universal host-defense pathway and protects mammalian species from various pathogens.
Abstract.
2020
Schaefer K, Dambuza IM, Dall’Angelo S, Yuecel R, Jaspars M, Trembleau L, Zanda M, Brown GD, Netea MG, Gow NAR, et al (2020). A Weakened Immune Response to Synthetic Exo-Peptides Predicts a Potential Biosecurity Risk in the Retrieval of Exo-Microorganisms.
Microorganisms,
8(7), 1066-1066.
Abstract:
A Weakened Immune Response to Synthetic Exo-Peptides Predicts a Potential Biosecurity Risk in the Retrieval of Exo-Microorganisms
The discovery of liquid water at several locations in the solar system raises the possibility that microbial life may have evolved outside Earth and as such could be accidently introduced into the Earth’s ecosystem. Unusual sugars or amino acids, like non-proteinogenic isovaline and α-aminoisobutyric acid that are vanishingly rare or absent from life forms on Earth, have been found in high abundance on non-terrestrial carbonaceous meteorites. It is therefore conceivable that exo-microorganisms might contain proteins that include these rare amino acids. We therefore asked whether the mammalian immune system would be able to recognize and induce appropriate immune responses to putative proteinaceous antigens that include these rare amino acids. To address this, we synthesised peptide antigens based on a backbone of ovalbumin and introduced isovaline and α-aminoisobutyric acid residues and demonstrated that these peptides can promote naïve OT-I cell activation and proliferation, but did so less efficiently than the canonical peptides. This is relevant to the biosecurity of missions that may retrieve samples from exoplanets and moons that have conditions that may be permissive for life, suggesting that accidental contamination and exposure to exo-microorganisms with such distinct proteomes might pose an immunological challenge.
Abstract.
Zhou X, Zafar H, Sephton-Clark P, Mohamed S, Chapuis A, Makarova M, MacCallum D, Drummond R, Dambuza I, Ballou E, et al (2020). Host environmental conditions induce small fungal cell size and alter population heterogeneity in <i>Cryptococcus neoformans</i>.
Abstract:
Host environmental conditions induce small fungal cell size and alter population heterogeneity in Cryptococcus neoformans
Fungal morphology significantly impacts the host response. Filamentation and tissue penetration by Candida and Aspergillus species are essential for virulence, while growth as a yeast allows the thermal dimorphic fungi Coccidiodes, Histoplasma, and Talaromyces to reside inside phagocytes and disseminate. The basidiomycete Cryptococcus neoformans exhibits an unusual yeast-to-titan transition thought to enhance pathogenicity by increasing fungal survival in the host lung and dissemination to the central nervous system. In a common laboratory strain (H99), in vitro and in vivo titan induction yields a heterogenous population including >10 μm titan cells, 5-7 μm yeast cells and 2-4 μm titanides. Previous reports have shown that titan cells are associated with enhanced virulence and the generation of aneuploid cells that facilitate stress adaptation and drug resistance, while small (>10 μm) cells are associated with increased dissemination. However, the relationship between titan cells, small cells, and titanides remains unclear. Here, we characterize titanides and small cells in H99 and three clinical isolates and show that titanides share the lipid membrane order of their titan mothers and the G 0 quiescent-like DNA staining of mating spores. In addition, we show that both titanizing and non-titanizing isolates exhibit altered capsule structure and PAMP exposure over time during in vitro culture, and generate aneuploidy in vivo. Author summary the human fungal pathogen Cryptococcus neoformans causes 200,000 HIV-associated deaths each year. In the lung, Cryptococcus makes an unusual yeast-to-titan morphological switch that contributes to disease development by altering immune polarization and introducing aneuploidy underlying host stress and drug resistance. Specifically, a proportion of 5 um haploid yeast endoreduplicate and swell, converting to large (> 10 um) polyploid titan cells that can then produce genetically distinct daughter cells. We recently developed an in vitro protocol for inducing large titan cells and additionally observed a novel small “titanide” cell type. Here we investigate the nature and origin of these small cells, demonstrating that they emerge during both in vitro and in vivo mouse-passaged titan induction in the well characterised lab strain H99 and are also apparent in a titanizing clinical isolate, Zc8. We show that these titanide cells share features with titan mothers (lipid order) and with spores produced during heterothalic mating. Finally, we show that the capacity of clinical isolates to produce both titan and titanide cells impacts aneuploidy and the emergence of drug resistance in vivo.
Abstract.
Speakman EA, Dambuza IM, Salazar F, Brown GD (2020). T Cell Antifungal Immunity and the Role of C-Type Lectin Receptors.
Trends Immunol,
41(1), 61-76.
Abstract:
T Cell Antifungal Immunity and the Role of C-Type Lectin Receptors.
Fungi can cause disease in humans, from mucocutaneous to life-threatening systemic infections. Initiation of antifungal immunity involves fungal recognition by pattern recognition receptors such as C-type lectin receptors (CLRs). These germline-encoded receptors trigger a multitude of innate responses including phagocytosis, fungal killing, and antigen presentation which can also shape the development of adaptive immunity. Recently, studies have shed light on how CLRs directly or indirectly modulate lymphocyte function. Moreover, CLR-mediated recognition of commensal fungi maintains homeostasis and prevents invasion from opportunistic commensals. We present an overview of current knowledge of antifungal T cell immune responses, with emphasis on the role of C-type lectins, and discuss how these receptors modulate these responses at different levels.
Abstract.
Author URL.
2019
Dambuza IM, Brown GD (2019). Fungi accelerate pancreatic cancer.
Nature,
574(7777), 184-185.
Author URL.
Marrero B, He C, Oh H-M, Ukwu UT, Yu C-R, Dambuza IM, Sun L, Egwuagu CE (2019). Persistent Activation of STAT3 Pathway in the Retina Induced Vision Impairment and Retinal Degenerative Changes in Ageing Mice.
Adv Exp Med Biol,
1185, 353-358.
Abstract:
Persistent Activation of STAT3 Pathway in the Retina Induced Vision Impairment and Retinal Degenerative Changes in Ageing Mice.
Neurotrophic factors can promote the survival of degenerating retinal cells through the activation of STAT3 pathway. Thus, augmenting STAT3 activation in the retina has been proposed as potential therapy for retinal dystrophies. On the other hand, aberrant activation of STAT3 pathway is oncogenic and implicated in diverse human diseases. Furthermore, the STAT3/SOCS3 axis has been shown to induce the degradation of rhodopsin during retinal inflammation. In this study, we generated and used mice with constitutive activation of STAT3 pathway in the retina to evaluate the safety and consequences of enhancing STAT3 activities in the retina as a potential treatment for retinal degenerative diseases. We show that long-term activation of the STAT3 pathway can induce retinal degenerative changes and also exacerbate uveitis and other intraocular inflammatory diseases. Mechanisms underlying the development of vision impairment in the STAT3c-Tg mice derived in part from STAT3-mediated inhibition of rhodopsin and overexpression of SOCS3 in the retina. These results suggest that much caution should be exercised in the use of STAT3 augmentation therapy for retinal dystrophies.
Abstract.
Author URL.
Baldassarre M, Solano-Collado V, Balci A, Colamarino RA, Dambuza IM, Reid DM, Wilson HM, Brown GD, Mukhopadhyay S, Dougan G, et al (2019). The Rab32/BLOC-3 dependent pathway mediates host- defence against different pathogens in human macrophages.
Haider M, Dambuza IM, Asamaphan P, Stappers M, Reid D, Yamasaki S, Brown GD, Gow NAR, Erwig LP (2019). The pattern recognition receptors dectin-2, mincle, and FcRγ impact the dynamics of phagocytosis of Candida, Saccharomyces, Malassezia, and Mucor species.
PLoS One,
14(8).
Abstract:
The pattern recognition receptors dectin-2, mincle, and FcRγ impact the dynamics of phagocytosis of Candida, Saccharomyces, Malassezia, and Mucor species.
Phagocytosis is a receptor-mediated process critical to innate immune clearance of pathogens. It proceeds in a regulated sequence of stages: (a) migration of phagocytes towards pathogens, (b) recognition of PAMPs and binding through PRRs, (c) engulfment and internalisation into phagosomes, (d) phagosome maturation, and (e) killing of pathogen or host cells. However, little is known about the role that individual receptors play in these discrete stages in the recognition of fungal cells. In a previous study, we found that dectin-2 deficiency impacted some but not all stages of macrophage-mediated phagocytosis of Candida glabrata. Because the C-type lectin receptor dectin-2 critically requires coupling to the FcRγ chain for signalling, we hypothesised that this coupling may be important for regulating phagocytosis of fungal cargo. We therefore examined how deficiency in FcRγ itself or two receptors to which it couples (dectin-2 and mincle) impacts phagocytosis of six fungal organisms representing three different fungal taxa. Our data show that deficiency in these proteins impairs murine bone marrow-derived macrophage migration, engulfment, and phagosome maturation, but not macrophage survival. Therefore, FcRγ engagement with selective C-type lectin receptors (CLRs) critically affects the spatio-temporal dynamics of fungal phagocytosis.
Abstract.
Author URL.
2018
Stappers MHT, Clark AE, Aimanianda V, Bidula S, Reid DM, Asamaphan P, Hardison SE, Dambuza IM, Valsecchi I, Kerscher B, et al (2018). Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus.
Nature,
555(7696), 382-386.
Abstract:
Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus
Resistance to infection is critically dependent on the ability of pattern recognition receptors to recognize microbial invasion and induce protective immune responses. One such family of receptors are the C-type lectins, which are central to antifungal immunity. These receptors activate key effector mechanisms upon recognition of conserved fungal cell-wall carbohydrates. However, several other immunologically active fungal ligands have been described; these include melanin, for which the mechanism of recognition is hitherto undefined. Here we identify a C-type lectin receptor, melanin-sensing C-type lectin receptor (MelLec), that has an essential role in antifungal immunity through recognition of the naphthalene-diol unit of 1,8-dihydroxynaphthalene (DHN)-melanin. MelLec recognizes melanin in conidial spores of Aspergillus fumigatus as well as in other DHN-melanized fungi. MelLec is ubiquitously expressed by CD31+ endothelial cells in mice, and is also expressed by a sub-population of these cells that co-express epithelial cell adhesion molecule and are detected only in the lung and the liver. In mouse models, MelLec was required for protection against disseminated infection with A. fumigatus. In humans, MelLec is also expressed by myeloid cells, and we identified a single nucleotide polymorphism of this receptor that negatively affected myeloid inflammatory responses and significantly increased the susceptibility of stem-cell transplant recipients to disseminated Aspergillus infections. MelLec therefore recognizes an immunologically active component commonly found on fungi and has an essential role in protective antifungal immunity in both mice and humans.
Abstract.
Stappers MHT, Clark AE, Aimanianda V, Bidula S, Reid DM, Asamaphan P, Hardison SE, Dambuza IM, Valsecchi I, Kerscher B, et al (2018). Recognition of DHN-melanin by the C-type lectin, MelLec, is required for protective immunity to Aspergillus fumigatus.
Author URL.
2017
Dambuza IM, Levitz SM, Netea MG, Brown GD (2017). Fungal recognition and host defense mechanisms. In (Ed)
The Fungal Kingdom, 887-902.
Abstract:
Fungal recognition and host defense mechanisms
Abstract.
Choi IK, Dambuza IM, He C, Yu C-R, Uche AN, Mattapallil MJ, Caspi RR, Egwuagu CE (2017). IL-12p35 Inhibits Neiiroinflarnmation and Ameliorates Autoimmune Encephalomyelitis.
Author URL.
Choi JK, Dambuza IM, He C, Yu C-R, Uche AN, Mattapallil MJ, Caspi RR, Egwuagu CE (2017). IL-12p35 Inhibits Neuroinflammation and Ameliorates Autoimmune Encephalomyelitis.
FRONTIERS IN IMMUNOLOGY,
8 Author URL.
Choi JK, Dambuza IM, He C, Yu C-R, Uche AN, Mattapallil MJ, Caspi RR, Egwuagu CE (2017). IL-12p35 Inhibits Neuroinflammation and Ameliorates Autoimmune Encephalomyelitis. The Journal of Immunology, 198(1_Supplement), 72.1-72.1.
Dambuza IM, He C, Choi JK, Yu C-R, Wang R, Mattapallil MJ, Wingfield PT, Caspi RR, Egwuagu CE (2017). IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease.
NATURE COMMUNICATIONS,
8 Author URL.
Dambuza IM, Drake T, Chapuis A, Taylor-Smith L, LeGrave N, Rasmussen T, Fisher MC, Bicanic T, Harrison TS, Jaspars M, et al (2017). The Cryptococcus neoformans Titan cell is an inducible and regulated morphotype underlying pathogenesis.
2016
Dambuza IM, Keeton R, Hsu N-J, Allie N, Quesniaux VFJ, Ryffel B, Jacobs M (2016). Persistent p55TNFR expression impairs T cell responses during chronic tuberculosis and promotes reactivation.
SCIENTIFIC REPORTS,
6 Author URL.
Kerscher B, Dambuza IM, Christofi M, Reid DM, Yamasaki S, Willment JA, Brown GD (2016). Signalling through MyD88 drives surface expression of the mycobacterial receptors MCL (Clecsf8, Clec4d) and Mincle (Clec4e) following microbial stimulation.
Microbes and Infection,
18(7-8), 505-509.
Abstract:
Signalling through MyD88 drives surface expression of the mycobacterial receptors MCL (Clecsf8, Clec4d) and Mincle (Clec4e) following microbial stimulation
The heterodimeric mycobacterial receptors, macrophage C-type lectin (MCL) and macrophage inducible C-type lectin (Mincle), are upregulated at the cell surface following microbial challenge, but the mechanisms underlying this response are unclear. Here we report that microbial stimulation triggers Mincle expression through the myeloid differentiation primary response gene 88 (MyD88) pathway; a process that does not require MCL. Conversely, we show that MCL is constitutively expressed but retained intracellularly until Mincle is induced, whereupon the receptors form heterodimers which are translocated to the cell surface. Thus this “two-step” model for induction of these key receptors provides new insights into the underlying mechanisms of anti-mycobacterial immunity.
Abstract.
2015
Dambuza IM, Brown GD (2015). C-type lectins in immunity: recent developments.
CURRENT OPINION IN IMMUNOLOGY,
32, 21-27.
Author URL.
Wang X, Wei Y, Liu X, Xing C, Han G, Chen G, Hou C, Dambuza IM, Shen B, Li Y, et al (2015). IL-15-secreting gamma delta T cells induce memory T cells in experimental allergic encephalomyelitis (EAE) mice.
MOLECULAR IMMUNOLOGY,
66(2), 402-408.
Author URL.
Egwuagu CE, Sun L, Kim S-H, Dambuza IM (2015). Ocular Inflammatory Diseases: Molecular Pathogenesis and Immunotherapy.
CURRENT MOLECULAR MEDICINE,
15(6), 517-528.
Author URL.
2014
Dambuza I, Yu C-R, Wang R-X, Kim S-Y, Mahdi R, Dolinska M, Sergeev Y, Wingfield P, Egwuagu C (2014). IL-12p35 single chain subunit antagonizes IL-6 mediated STAT1 and STAT3 activation and prevents expansion of Th17 cells in experimental autoimmune uveitis (CCR1P.246). The Journal of Immunology, 192(1_Supplement), 48.6-48.6.
Wang R-X, Yu C-R, Dambuza IM, Mahdi RM, Dolinska MB, Sergeev YV, Wingfield PT, Kim S-H, Egwuagu CE (2014). Interleukin-35 induces regulatory B cells that suppress autoimmune disease.
NATURE MEDICINE,
20(6), 633-641.
Author URL.
Keeton R, Allie N, Dambuza I, Abel B, Hsu N-J, Sebesho B, Randall P, Burger P, Fick E, Quesniaux VFJ, et al (2014). Soluble TNFRp75 regulates host protective immunity against Mycobacterium tuberculosis. Journal of Clinical Investigation, 124(4), 1537-1551.
Yu C, Dambuza IM, Kim S-H, Mahdi RM, Egwuagu C (2014). Suppression of experimental autoimmune uveitis (EAU) and recovery from uveitis correlate with expansion of regulatory B cells (Breg).
Author URL.
2013
Yu C-R, Dambuza IM, Lee Y-J, Frank GM, Egwuagu CE (2013). STAT3 Regulates Proliferation and Survival of CD8(+) T Cells: Enhances Effector Responses to HSV-1 Infection, and Inhibits IL-10(+) Regulatory CD8(+) T Cells in Autoimmune Uveitis.
MEDIATORS OF INFLAMMATION,
2013 Author URL.
2012
Amadi-Obi A, Yu C-R, Dambuza I, Kim S-H, Marrero B, Egwuagu CE (2012). Interleukin 27 Induces the Expression of Complement Factor H (CFH) in the Retina. PLoS ONE, 7(9), e45801-e45801.
Oh H-M, Yu C-R, Dambuza I, Marrero B, Egwuagu CE (2012). STAT3 Protein Interacts with Class O Forkhead Transcription Factors in the Cytoplasm and Regulates Nuclear/Cytoplasmic Localization of FoxO1 and FoxO3a Proteins in CD4+ T Cells. Journal of Biological Chemistry, 287(36), 30436-30443.
2011
Dambuza I, Keeton R, Allie N, Hsu N-J, Randall P, Sebesho B, Fick L, Quesniaux VJF, Jacobs M (2011). Reactivation of M. tuberculosis Infection in Trans-Membrane Tumour Necrosis Factor Mice. PLoS ONE, 6(11), e25121-e25121.
2008
Dambuza I, Allie N, Fick L, Johnston N, Fremond C, Mitchell J, Quesniaux VFJ, Ryffel B, Jacobs M (2008). Efficacy of membrane TNF mediated host resistance is dependent on mycobacterial virulence. Tuberculosis, 88(3), 221-234.
2005
Fremond C, Allie N, Dambuza I, Grivennikov SI, Yeremeev V, Quesniaux VFJ, Jacobs M, Ryffel B (2005). Membrane TNF confers protection to acute mycobacterial infection.
Respiratory Research,
6(1).
Abstract:
Membrane TNF confers protection to acute mycobacterial infection
AbstractBackgroundTumour necrosis factor (TNF) is crucial for the control of mycobacterial infection as TNF deficient (KO) die rapidly of uncontrolled infection with necrotic pneumonia. Here we investigated the role of membrane TNF for host resistance in knock-in mice with a non-cleavable and regulated allele (mem-TNF).MethodsC57BL/6, TNF KO and mem-TNF mice were infected withM. tuberculosisH37Rv (Mtbat 100 CFU by intranasal administration) and the survival, bacterial load, lung pathology and immunological parameters were investigated. Bone marrow and lymphocytes transfers were used to test the role of membrane TNF to confer resistance to TNF KO mice.ResultsWhile TNF-KO mice succumbed to infection within 4–5 weeks, mem-TNF mice recruited normally T cells and macrophages, developed mature granuloma in the lung and controlled acuteMtbinfection. However, during the chronic phase of infection mem-TNF mice succumbed to disseminated infection with necrotic pneumonia at about 150 days. Reconstitution of irradiated TNF-KO mice with mem-TNF derived bone marrow cells, but not with lymphocytes, conferred host resistance toMtbinfection in TNF-KO mice.ConclusionMembrane expressed TNF is sufficient to allow cell-cell signalling and control of acuteMtbinfection. Bone marrow cells, but not lymphocytes from mem-TNF mice confer resistance to infection in TNF-KO mice. Long-term infection control with chronic inflammation likely disrupting TNF mediated cell-cell signalling, additionally requires soluble TNF.
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