Imperial College London

DrFranzPuttur

Faculty of MedicineNational Heart & Lung Institute

Lecturer in Early Life Airways Disease
 
 
 
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f.puttur

 
 
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Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
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27 results found

Joulia RPG, Puttur F, Stölting H, Traves W, Entwistle L, Voitovich A, Garcia Martín M, Al-Sahaf M, Bonner K, Scotney E, Molyneaux P, Hewitt R, Walker S, Yates L, Saglani S, Lloyd Cet al., 2024, Mast cell activation disrupts interactions between endothelial cells and pericytes during early life allergic asthma, Journal of Clinical Investigation, ISSN: 0021-9738

Journal article

Hewitt R, Puttur F, Gaboriau D, Fercoq F, Fresquet M, Traves W, Yates LL, Walker S, Molyneaux P, Kemp S, Nicholson A, Rice A, Roberts E, Lennon R, Carlin L, Byrne A, Maher T, Lloyd Cet al., 2023, Lung extracellular matrix modulates KRT5+ basal cell activity in pulmonary fibrosis, Nature Communications, Vol: 14, ISSN: 2041-1723

Aberrant expansion of KRT5+ basal cells in the distal lung accompanies progressive alveolar epithelial cell loss and tissue remodelling during fibrogenesis in idiopathic pulmonary fibrosis (IPF). The mechanisms determining activity of KRT5+ cells in IPF have not been delineated. Here, we reveal a potential mechanism by which KRT5+ cells migrate within the fibrotic lung, navigating regional differences in collagen topography. In vitro, KRT5+ cell migratory characteristics and expression of remodelling genes are modulated by extracellular matrix (ECM) composition and organisation. Mass spectrometry- based proteomics revealed compositional differences in ECM components secreted by primary human lung fibroblasts (HLF) from IPF patients compared to controls. Over-expression of ECM glycoprotein, Secreted Protein Acidic and Cysteine Rich (SPARC) in the IPF HLF matrix restricts KRT5+ cell migration in vitro. Together, our findings demonstrate how changes to the ECM in IPF directly influence KRT5+ cell behaviour and function contributing to remodelling events in the fibrotic niche.

Journal article

Puttur F, Lloyd CM, 2023, Breathing easy: Dopamine quenches the ILC2 flame, IMMUNITY, Vol: 56, Pages: 229-231, ISSN: 1074-7613

Journal article

Pyle CJ, Labeur-Iurman L, Groves HT, Puttur F, Lloyd CM, Tregoning JS, Harker JAet al., 2021, Enhanced IL-2 in early life limits the development of TFH and protective antiviral immunity, Journal of Experimental Medicine, Vol: 218, ISSN: 0022-1007

T follicular helper cell (TFH)-dependent antibody responses are critical for long-term immunity. Antibody responses are diminished in early life, limiting long-term protective immunity and allowing prolonged or recurrent infection, which may be important for viral lung infections that are highly prevalent in infancy. In a murine model using respiratory syncytial virus (RSV), we show that TFH and the high-affinity antibody production they promote are vital for preventing disease on RSV reinfection. Following a secondary RSV infection, TFH-deficient mice had significantly exacerbated disease characterized by delayed viral clearance, increased weight loss, and immunopathology. TFH generation in early life was compromised by heightened IL-2 and STAT5 signaling in differentiating naive T cells. Neutralization of IL-2 during early-life RSV infection resulted in a TFH-dependent increase in antibody-mediated immunity and was sufficient to limit disease severity upon reinfection. These data demonstrate the importance of TFH in protection against recurrent RSV infection and highlight a mechanism by which this is suppressed in early life.

Journal article

Helen S, Walker SA, Puttur F, Saglani S, Lloyd CMet al., 2021, LSC-2021-Epidermal growth factor receptor in airway remodelling during allergic airway disease - divergent roles during early life and adulthood?, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Farias A, Soto A, Puttur F, Goldin CJ, Sosa S, Gil C, Goldbaum FA, Berguer PMet al., 2021, A TLR4 agonist improves immune checkpoint blockade treatment by increasing the ratio of effector to regulatory cells within the tumor microenvironment, SCIENTIFIC REPORTS, Vol: 11, ISSN: 2045-2322

Journal article

Branchett W, Stoelting H, Oliver R, Walker S, Puttur F, Gregory L, Gabrysova L, Wilson M, O'Garra A, Lloyd Cet al., 2020, A T cell-myeloid IL-10 axis regulates pathogenic IFN-γ-dependent immunity in a mouse model of type 2-low asthma, Journal of Allergy and Clinical Immunology, Vol: 145, Pages: 666-678.e9, ISSN: 0091-6749

BackgroundAlthough originally defined as a type 2 (T2) immune-mediated condition, non-T2 cytokines, such as IFN-γ and IL-17A, have been implicated in asthma pathogenesis, particularly severe disease. IL-10 regulates T helper (Th) cell phenotypes and can dampen T2 immunity to allergens, but its functions in controlling non-T2 cytokine responses in asthma are unclear. Objective: Determine how IL-10 regulates the balance of Th cell responses to inhaled allergen.MethodsAllergic airway disease (AAD) was induced in wild-type, IL-10 reporter and conditional IL-10 or IL-10 receptor α (IL-10Rα) knockout mice, by repeated intranasal administration of house dust mite (HDM). IL-10 and IFN-γ signalling were disrupted using blocking antibodies.ResultsRepeated HDM inhalation induced a mixed IL-13/IL-17A response and accumulation of IL-10-producing FoxP3- effector CD4+ T cells in the lungs. Ablation of T cell-derived IL-10 increased the IFN-γ and IL-17A response to HDM, reducing IL-13 levels and airway eosinophilia without affecting IgE or airway hyperresponsiveness. The increased IFN-γ response could be recapitulated by IL-10Rα deletion in CD11c+ myeloid cells or local IL-10Rα blockade. Disruption of the T cell-myeloid IL-10 axis resulted in elevated pulmonary monocyte-derived dendritic cell numbers and increased IFN-γ-dependent expression of CXCR3 ligands by airway macrophages, suggestive of a feedforward loop of Th1 cell recruitment. Augmented IFN-γ responses in the HDM AAD model were accompanied by increased disruption of airway epithelium, which was reversed by therapeutic blockade of IFN-γ.ConclusionsIL-10 from effector T cells signals to CD11c+ myeloid cells to suppress an atypical and pathogenic IFN-γ response to inhaled HDM.

Journal article

Entwistle L, Gregory L, Oliver R, Branchett W, Puttur F, Lloyd Cet al., 2020, Pulmonary group 2 innate lymphoid cell phenotype is context specific: Determining the effect of strain, location and stimuli, Frontiers in Immunology, Vol: 10, ISSN: 1664-3224

Group 2 innate lymphoid cells (ILC2s) are enriched at mucosal sites, including the lung, and play a central role in type 2 immunity and maintaining tissue homeostasis. As a result, since their discovery in 2010, research into ILC2s has increased markedly. Numerous strategies have been used to define ILC2s by flow cytometry, often utilizing different combinations of surface markers despite their expression being variable and context-dependent. In this study, we sought to generate a comprehensive characterization of pulmonary ILC2s, identifying stable and context specific markers from different pulmonary compartments following different airway exposures in different strains of mice. Our analysis revealed that pulmonary ILC2 surface marker phenotype is heterogeneous and is influenced by mouse strain, pulmonary location, in vivo treatment/exposure and ex vivo stimulation. Therefore, we propose that a lineage negative cell expressing CD45 and Gata3 defines an ILC2, and subsequent surface marker expression should be used to describe their phenotype in context-specific scenarios.

Journal article

Entwistle LJ, Puttur F, Gregory LG, Lloyd CMet al., 2020, Group 2 ILC Functional Assays in Allergic Airway Inflammation, INNATE LYMPHOID CELLS, Vol: 2121, Pages: 99-114, ISSN: 1064-3745

Journal article

Hewitt RJ, Graham C, Perez-Lloret J, Ghai PA, Ogger PP, Kemp SV, Molyneaux PL, Puttur F, Byrne AJ, Maher TM, O'Garra A, Lloyd CMet al., 2020, A Transcriptomic Profile of the Proximal Airway Epithelial-Immune Niche in Idiopathic Pulmonary Fibrosis, Virtual International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Patel DF, Peiro T, Bruno N, Vuononvirta J, Akthar S, Puttur F, Pyle CJ, Suveizdyte K, Walker SA, Singanayagam A, Carlin LM, Gregory LG, Lloyd CM, Snelgrove Ret al., 2019, Neutrophils restrain allergic airway inflammation by limiting ILC2 function and monocyte-dendritic cell antigen presentation, Science Immunology, Vol: 4, Pages: 1-18, ISSN: 2470-9468

Neutrophil mobilization, recruitmentand clearancemust be tightly regulated asover-exuberant neutrophilic inflammation isimplicated in the pathology of chronic diseases, including asthma. Efforts to target neutrophilstherapeutically have failed to consider theirpleiotropic functions and theimplications of disrupting fundamental regulatory pathways that govern their turnover duringhomeostasisand inflammation.Using thehouse dust mite(HDM)model of allergic airways disease, we demonstrate that neutrophil depletion unexpectedly resulted in exacerbated TH2 inflammation, epithelial remodelling and airway resistance. Mechanistically, this was attributable to astriking increase insystemic G-CSF concentrations, which are ordinarily negatively regulated in the periphery by transmigrated lung neutrophils. Intriguingly, we found that increasedG-CSF augmented allergic sensitization in HDM exposed animals bydirectly acting on airway ILC2s toelicitcytokine production.Moreover, increased systemic G-CSF promoted expansion of bone marrow monocyte progenitor populations, which resulted in enhanced antigen presentation by an augmented peripheral monocyte-derived dendritic cell pool.By modelling the effects of neutrophil depletion, our studies have therefore uncovered previously unappreciated roles for G-CSF in modulating ILC2 function and antigen presentation. More broadly,they highlight an unexpected regulatory role for neutrophils in limiting TH2 allergic airway inflammation.

Journal article

Lloyd C, Puttur F, Denney L, Gregory L, Vuononvirta J, Oliver R, McGhee E, Pease J, Krummel MF, Headley MB, Carlin Let al., 2019, Pulmonary environmental cues drive group 2 innate lymphoid cell dynamics in mice and humans, Science Immunology, Vol: 4, ISSN: 2470-9468

Group 2 innate lymphoid cells (ILC2s) are enriched in mucosal tissues (e.g., lung) and respond to epithelial cell–derived cytokines initiating type 2 inflammation. During inflammation, ILC2 numbers are increased in the lung. However, the mechanisms controlling ILC2 trafficking and motility within inflamed lungs remain unclear and are crucial for understanding ILC2 function in pulmonary immunity. Using several approaches, including lung intravital microscopy, we demonstrate that pulmonary ILC2s are highly dynamic, exhibit amoeboid-like movement, and aggregate in the lung peribronchial and perivascular spaces. They express distinct chemokine receptors, including CCR8, and actively home to CCL8 deposits located around the airway epithelium. Within lung tissue, ILC2s were particularly motile in extracellular matrix–enriched regions. We show that collagen-I drives ILC2 to markedly change their morphology by remodeling their actin cytoskeleton to promote environmental exploration critical for regulating eosinophilic inflammation. Our study provides previously unappreciated insights into ILC2 migratory patterns during inflammation and highlights the importance of environmental guidance cues in the lung in controlling ILC2 dynamics.

Journal article

Puttur F, Denney L, Gregory L, Vuononvirta J, Oliver R, Entwistle L, Walker S, Headley M, McGhee E, Pease J, Krummel M, Carlin L, Lloyd Cet al., 2019, Pulmonary environmental cues drive group 2 innate lymphoid cell dynamics in mice and humans, Science Immunology, ISSN: 2470-9468

Journal article

Nagakumar P, Puttur F, Gregory LG, Denney L, Fleming L, Bush A, Lloyd CM, Saglani Set al., 2019, Pulmonary type2 innate lymphoid cells in paediatric severe asthma: phenotype and response to steroids, European Respiratory Journal, Vol: 54, Pages: 1-14, ISSN: 0903-1936

Children with severe therapy resistant asthma (STRA) have poor control despite maximal treatment, while those with difficult asthma (DA) have poor control from failure to implement basic management including adherence to therapy. Although recognised as clinically distinct, the airway molecular phenotype, including the role of ILCs and their response to steroids in DA and STRA is unknown.Immunophenotyping of sputum and blood ILCs and T cells from STRA, DA and non-asthmatic controls was undertaken. Leukocytes were analysed longitudinally pre and post intramuscular triamcinolone in children with STRA. Cultured ILCs were also evaluated to assess steroid responsiveness in vitroAirway eosinophils, Th2 cells and ILC2s were significantly higher in STRA patients compared to DA and disease controls, while IL-17+ lymphoid cells were similar. ILC2s and Th2 cells were significantly reduced in vivo following intramuscular triamcinolone and in vitro with steroids. Asthma attacks and symptoms also reduced after systemic steroids despite persistence of steroid resistant IL-17+ cells and eosinophils.Paediatric STRA and DA have distinct airway molecular phenotypes with STRA characterised by elevated type2 cells. Systemic corticosteroids but not maintenance inhaled steroids resulted in improved symptom control and exacerbations concomitant with a reduction in functional ILC2s despite persistently elevated IL-17+ lymphoid cells.

Journal article

Solmaz G, Puttur F, Francozo M, Lindenberg M, Guderian M, Swallow M, Duhan V, Khairnar V, Kalinke U, Ludewig B, Clausen BE, Wagner H, Lang KS, Sparwasser TDet al., 2019, TLR7 controls VSV replication in CD169(+) SCS macrophages and associated viral neuroinvasion, Frontiers in Immunology, Vol: 10, ISSN: 1664-3224

Vesicular stomatitis virus (VSV) is an insect-transmitted rhabdovirus that is neurovirulent in mice. Upon peripheral VSV infection, CD169+ subcapsular sinus (SCS) macrophages capture VSV in the lymph, support viral replication, and prevent CNS neuroinvasion. To date, the precise mechanisms controlling VSV infection in SCS macrophages remain incompletely understood. Here, we show that Toll-like receptor-7 (TLR7), the main sensing receptor for VSV, is central in controlling lymph-borne VSV infection. Following VSV skin infection, TLR7−/− mice display significantly less VSV titers in the draining lymph nodes (dLN) and viral replication is attenuated in SCS macrophages. In contrast to effects of TLR7 in impeding VSV replication in the dLN, TLR7−/− mice present elevated viral load in the brain and spinal cord highlighting their susceptibility to VSV neuroinvasion. By generating novel TLR7 floxed mice, we interrogate the impact of cell-specific TLR7 function in anti-viral immunity after VSV skin infection. Our data suggests that TLR7 signaling in SCS macrophages supports VSV replication in these cells, increasing LN infection and may account for the delayed onset of VSV-induced neurovirulence observed in TLR7−/− mice. Overall, we identify TLR7 as a novel and essential host factor that critically controls anti-viral immunity to VSV. Furthermore, the novel mouse model generated in our study will be of valuable importance to shed light on cell-intrinsic TLR7 biology in future studies.

Journal article

Gregory L, Lloyd C, Puttur F, 2019, Airway macrophages as the guardians of tissue repair in the lung, Immunology and Cell Biology, ISSN: 1440-1711

Journal article

Saglani S, Gregory LG, Manghera AK, Branchett WJ, Uwadiae F, Entwistle LJ, Oliver RA, Vasiliou JE, Sherburn R, Lui S, Puttur F, Voehringer D, Walker SA, Buckley J, Grychtol R, Fainardi V, Denney L, Byrnes A, von Mutius E, Bush A, Lloyd CMet al., 2018, Inception of early life allergen induced airway hyperresponsiveness is reliant on IL-13+CD4+ T cells, Science Immunology, Vol: 3, Pages: 1-12, ISSN: 2470-9468

Airway hyperresponsiveness (AHR) is a critical feature of wheezing and asthma in children, but the initiating immune mechanisms remain unconfirmed. We demonstrate that both recombinant interleukin-33 (rIL-33) and allergen [house dust mite (HDM) or Alternaria alternata] exposure from day 3 of life resulted in significantly increased pulmonary IL-13+CD4+ T cells, which were indispensable for the development of AHR. In contrast, adult mice had a predominance of pulmonary LinnegCD45+CD90+IL-13+ type 2 innate lymphoid cells (ILC2s) after administration of rIL-33. HDM exposure of neonatal IL-33 knockout (KO) mice still resulted in AHR. However, neonatal CD4creIL-13 KO mice (lacking IL-13+CD4+ T cells) exposed to allergen from day 3 of life were protected from AHR despite persistent pulmonary eosinophilia, elevated IL-33 levels, and IL-13+ ILCs. Moreover, neonatal mice were protected from AHR when inhaled Acinetobacter lwoffii (an environmental bacterial isolate found in cattle farms, which is known to protect from childhood asthma) was administered concurrent with HDM. A. lwoffii blocked the expansion of pulmonary IL-13+CD4+ T cells, whereas IL-13+ ILCs and IL-33 remained elevated. Administration of A. lwoffii mirrored the findings from the CD4creIL-13 KO mice, providing a translational approach for disease protection in early life. These data demonstrate that IL-13+CD4+ T cells, rather than IL-13+ ILCs or IL-33, are critical for inception of allergic AHR in early life.

Journal article

Puttur F, Francozo M, Solmaz G, Bueno C, Lindenberg M, Gohmert M, Swallow M, Tufa D, Jacobs R, Lienenklaus S, Kuehl AA, Borkner L, Cicin-Sain L, Holzmann B, Wagner H, Berod L, Sparwasser Tet al., 2016, Conventional dendritic cells confer protection against mouse cytomegalovirus infection via TLR9 and MyD88 signaling, Cell Reports, Vol: 17, Pages: 1113-1127, ISSN: 2211-1247

Cytomegalovirus (CMV) is an opportunistic virus severely infecting immunocompromised individuals. In mice, endosomal Toll-like receptor 9 (TLR9) and downstream myeloid differentiation factor 88 (MyD88) are central to activating innate immune responses against mouse CMV (MCMV). In this respect, the cell-specific contribution of these pathways in initiating anti-MCMV immunity remains unclear. Using transgenic mice, we demonstrate that TLR9/MyD88 signaling selectively in CD11c+ dendritic cells (DCs) strongly enhances MCMV clearance by boosting natural killer (NK) cell CD69 expression and IFN-γ production. In addition, we show that in the absence of plasmacytoid DCs (pDCs), conventional DCs (cDCs) promote robust NK cell effector function and MCMV clearance in a TLR9/MyD88-dependent manner. Simultaneously, cDC-derived IL-15 regulates NK cell degranulation by TLR9/MyD88-independent mechanisms. Overall, we compartmentalize the cellular contribution of TLR9 and MyD88 signaling in individual DC subsets and evaluate the mechanism by which cDCs control MCMV immunity.

Journal article

Dudek M, Puttur F, Arnold-Schrauf C, Kuehl AA, Holzmann B, Henriques-Normark B, Berod L, Sparwasser Tet al., 2015, Lung epithelium and myeloid cells cooperate to clear acute pneumococcal infection, Mucosal Immunology, Vol: 9, Pages: 1288-1302, ISSN: 1933-0219

The Gram-positive bacterium Streptococcus pneumoniae causes life-threatening infections, especially among immunocompromised patients. The host’s immune system senses S. pneumoniae via different families of pattern recognition receptors, in particular the Toll-like receptor (TLR) family that promotes immune cell activation. Yet, while single TLRs are dispensable for initiating inflammatory responses against S. pneumoniae, the central TLR adapter protein myeloid differentiation factor 88 (MyD88) is of vital importance, as MyD88-deficient mice succumb rapidly to infection. Since MyD88 is ubiquitously expressed in hematopoietic and non-hematopoietic cells, the extent to which MyD88 signaling is required in different cell types to control S. pneumoniae is unknown. Therefore, we used novel conditional knockin mice to investigate the necessity of MyD88 signaling in distinct lung-resident myeloid and epithelial cells for the initiation of a protective immune response against S. pneumoniae. Here, we show that MyD88 signaling in lysozyme M (LysM)– and CD11c-expressing myeloid cells, as well as in pulmonary epithelial cells, is critical to restore inflammatory cytokine and antimicrobial peptide production, leading to efficient neutrophil recruitment and enhanced bacterial clearance. Overall, we show a novel synergistic requirement of compartment-specific MyD88 signaling in S. pneumoniae immunity.

Journal article

Unger WWJ, Mayer CT, Engels S, Hesse C, Perdicchio M, Puttur F, Streng-Ouwehand I, Litjens M, Kalay H, Berod L, Sparwasser T, van Kooyk Yet al., 2015, Antigen targeting to dendritic cells combined with transient regulatory T cell inhibition results in long-term tumor regression, OncoImmunology, Vol: 4, ISSN: 2162-4011

Therapeutic vaccinations against cancer are still largely ineffective. Major caveats are inefficient delivery of tumor antigens to dendritic cells (DCs) and excessive immune suppression by Foxp3+ regulatory T cells (Tregs), resulting in defective T cell priming and failure to induce tumor regression. To circumvent these problems we evaluated a novel combinatorial therapeutic strategy. We show that tumor antigen targeting to DC-SIGN in humanized hSIGN mice via glycans or specific antibodies induces superior T cell priming. Next, this targeted therapy was combined with transient Foxp3+ Treg depletion employing hSIGNxDEREG mice. While Treg depletion alone slightly delayed B16-OVA melanoma growth, only the combination therapy instigated long-term tumor regression in a substantial fraction of mice. This novel strategy resulted in optimal generation of antigen-specific activated CD8+ T cells which accumulated in regressing tumors. Notably, Treg depletion also allowed the local appearance of effector T cells specific for endogenous B16 antigens. This indicates that antitumor immune responses can be broadened by therapies aimed at controlling Tregs in tumor environments. Thus, transient inhibition of Treg-mediated immune suppression potentiates DC targeted antigen vaccination and tumor-specific immunity.

Journal article

Mayer CT, Ghorbani P, Nandan A, Dudek M, Arnold-Schrauf C, Hesse C, Berod L, Stueve P, Puttur F, Merad M, Sparwasser Tet al., 2014, Selective and efficient generation of functional Batf3-dependent CD103<SUP>+</SUP> dendritic cells from mouse bone marrow, BLOOD, Vol: 124, Pages: 3081-3091, ISSN: 0006-4971

Journal article

Lindenberg M, Solmaz G, Puttur F, Sparwasser Tet al., 2014, Mouse cytomegalovirus infection overrules T regulatory cell suppression on natural killer cells, Virology Journal, Vol: 11, ISSN: 1743-422X

BackgroundCytomegalovirus establishes lifelong persistency in the host and leads to life threatening situations in immunocompromised patients. FoxP3+ T regulatory cells (Tregs) critically control and suppress innate and adaptive immune responses. However, their specific role during MCMV infection, especially pertaining to their interaction with NK cells, remains incompletely defined.MethodsTo understand the contribution of Tregs on NK cell function during acute MCMV infection, we infected Treg depleted and undepleted DEREG mice with WT MCMV and examined Treg and NK cell frequency, number, activation and effector function in vivo.ResultsOur results reveal an increased frequency of activated Tregs within the CD4+ T cell population shortly after MCMV infection. Specific depletion of Tregs in DEREG mice under homeostatic conditions leads to an increase in NK cell number as well as to a higher activation status of these cells as compared with non-depleted controls. Interestingly, upon infection this effect on NK cells is completely neutralized in terms of cell frequency, CD69 expression and functionality with respect to IFN-γ production. Furthermore, composition of the NK cell population with regard to Ly49H expression remains unchanged. In contrast, absence of Tregs still boosts the general T cell response upon infection to a level comparable to the enhanced activation seen in uninfected mice. CD4+ T cells especially benefit from Treg depletion exhibiting a two-fold increase of CD69+ cells 40 h and IFN-γ+ cells 7 days p.i. while, MCMV infection per se induces robust CD8+ T cell activation which is also further augmented in Treg-depleted mice. Nevertheless, the viral burden in the liver and spleen remain unaltered upon Treg ablation during the course of infection.ConclusionsThus, MCMV infection abolishes Treg suppressing effects on NK cells whereas T cells benefit from their absence during acute infection. This study provides novel information in understandin

Journal article

Puttur F, Arnold-Schrauf C, Lahl K, Solmaz G, Lindenberg M, Mayer CT, Gohmert M, Swallow M, van Helt C, Schmitt H, Nitschke L, Lambrecht BN, Lang R, Messerle M, Sparwasser Tet al., 2013, Absence of siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance, PLoS Pathogens, Vol: 9, ISSN: 1553-7366

Plasmacytoid dendritic cells (pDCs) express the I-type lectin receptor Siglec-H and produce interferon a (IFNa), a critical antiviral cytokine during the acute phase of murine cytomegalovirus (MCMV) infection. The ligands and biological functions ofSiglec-H still remain incompletely defined in vivo. Thus, we generated a novel bacterial artificial chromosome (BAC)-transgenic ‘‘pDCre’’ mouse which expresses Cre recombinase under the control of the Siglec-H promoter. By crossing thesemice with a Rosa26 reporter strain, a representative fraction of Siglec-H+ pDCs is terminally labeled with red fluorescentprotein (RFP). Interestingly, systemic MCMV infection of these mice causes the downregulation of Siglec-H surfaceexpression. This decline occurs in a TLR9- and MyD88-dependent manner. To elucidate the functional role of Siglec-H duringMCMV infection, we utilized a novel Siglec-H deficient mouse strain. In the absence of Siglec-H, the low infection rate ofpDCs with MCMV remained unchanged, and pDC activation was still intact. Strikingly, Siglec-H deficiency induced asignificant increase in serum IFNa levels following systemic MCMV infection. Although Siglec-H modulates anti-viral IFNaproduction, the control of viral replication was unchanged in vivo. The novel mouse models will be valuable to shed furtherlight on pDC biology in future studies.

Journal article

Baru AM, Ganesh V, Krishnaswamy JK, Hesse C, Untucht C, Glage S, Behrens G, Mayer CT, Puttur F, Sparwasser Tet al., 2012, Absence of Foxp3(+) regulatory T cells during allergen provocation does not exacerbate murine allergic airway inflammation, PLoS ONE, Vol: 7, ISSN: 1932-6203

Regulatory T cells (Tregs) play a non-redundant role in maintenance of immune homeostasis. This is achieved bysuppressing both, priming of naı¨ve cells and effector cell functions. Although Tregs have been implicated in modulatingallergic immune responses, their influence on distinct phases of development of allergies remains unclear. In this study, byusing bacterial artificial chromosome (BAC)-transgenic Foxp3-DTR (DEREG) mice we demonstrate that the absence ofFoxp3+ Tregs during the allergen challenge surprisingly does not exacerbate allergic airway inflammation in BALB/c mice. Asgenetic disposition due to strain specificity may contribute significantly to development of allergies, we performed similarexperiment in C57BL/6 mice, which are less susceptible to allergy in the model of sensitization used in this study. We reportthat the genetic background does not influence the consequence of this depletion regimen. These results signify thetemporal regulation exerted by Foxp3+ Tregs in limiting allergic airway inflammation and may influence their application aspotential therapeutics.

Journal article

Berod L, Puttur F, Huehn J, Sparwasser Tet al., 2012, Tregs in infection and vaccinology: heroes or traitors?, Microbial Biotechnology, Vol: 5, Pages: 260-269, ISSN: 1751-7915

The development of effective vaccines against life‐threatening pathogens in human diseases represents one of the biggest challenges in biomedical science. Vaccines traditionally make use of the body's own immune armoury to combat pathogens. Yet, while our immune system is mostly effective in eliminating or controlling a diverse range of microorganisms, its responses are incomplete or somewhat limited in several other cases. How immune responses are restrained during certain infections has been a matter of debate for many years. The discovery of regulatory T cells (Tregs), an immune cell type that plays a central role in maintaining immune homeostasis and controlling appropriate immune responses, has shed light into many questions. Indeed, it has been proposed that while Tregs might be beneficial in preventing excessive tissue damage during infection, they might also favour pathogen persistence by restraining effector immune responses. In addition, Tregs are believed to limit immune responses upon vaccination. Different strategies have been pursued to circumvent Treg activity during immunization, but the lack of specific tools for their study has led sometimes to controversial conclusions. With the advent of novel mouse models that allow specific depletion and/or tracking of Treg populations in vivo, novel aspects of Treg biology during infection have been unravelled. In this review, we describe the new advances in understanding Treg biology during infection and evaluate Treg depletion as a novel adjuvant strategy for vaccination.

Journal article

Schevzov G, Fath T, Vrhovski B, Vlahovich N, Rajan S, Hook J, Joya JE, Lemckert F, Puttur F, Lin JJ-C, Hardeman EC, Wieczorek DF, O'Neill GM, Gunning PWet al., 2008, Divergent regulation of the sarcomere and the cytoskeleton, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 283, Pages: 275-283

Journal article

Schevzov G, Vrhovski B, Bryce NS, Elmir S, Qiu M, Yang N, Verrills NM, Kavallaris M, Puttur F, Hardeman E, Gunning Pet al., 2004, Tropomyosin antibodies identify functionally distinct populations of actin filaments, Annual Meeting of the American-Society-for-Cell-Biology, Publisher: AMER SOC CELL BIOLOGY, Pages: 143A-143A, ISSN: 1059-1524

Conference paper

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