Publications by category
Journal articles
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, 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.
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.
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
© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. 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.
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.
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, 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
© 2016 the Authors 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.
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.
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-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 Author URL.
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.
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.
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.
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).
Conferences
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.
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.
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.
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, 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.
2019
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
© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. 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
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.
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.
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
© 2016 the Authors 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
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 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).