Medical Microbiology Commons^™

Holobiont Nutrition: Considering The Role Of The Gastrointestinal Microbiota In The Health Benefits Of Whole Grains, Jens Walter, Ines Martinez, Devin J. Rose

Food for Health: Publications

Intake of whole grains and other food products high in dietary fiber have long been linked to the prevention of chronic diseases associated with inflammation. A contribution of the gastrointestinal microbiota to these effects has been suggested, but little is known on how whole grains interact with gut bacteria. We have recently published the first human trial that made use of next-generation sequencing to determine the effect of whole grains (whole grain barley, brown rice or a mixture of the two) on fecal microbiota structure and tested for associations between the gut microbiota and blood markers of inflammation, glucose and …

Neisseria Oralis Sp. Nov., Isolated From Healthy Gingival Plaque And Clinical Samples, William J. Wolfgang, Teresa V. Passaretti, Reashma Jose, Jocelyn Cole, An Coorevits, Andrea N. Carpenter, Sherly Jose, Anita Van Landschoot, Jacques Izard, Donna J. Kohlerschmidt, Peter Vandamme, Floyd E. Dewhirst, Mark A. Fisher, Kimberlee A. Musser

Department of Food Science and Technology: Faculty Publications

A polyphasic analysis was undertaken of seven independent isolates of gram-negative cocci collected from pathological clinical samples from New York, Louisiana, Florida, and Illinois and healthy subgingival plaque from a patient in Virginia, USA. The 16S rRNA gene sequence similarity among these isolates was 99.7–100 %, and the closest species with a validly published name was Neisseria lactamica (96.9 % similarity to the type strain). DNA–DNA hybridization confirmed that these isolates are of the same species and are distinct from their nearest phylogenetic neighbor, N. lactamica. Phylogenetic analysis of 16S and 23S rRNA gene sequences indicated that the …

Gut Microbiome Composition Is Linked To Whole Grain-Induced Immunological Improvements, Ines Martinez, James M. Lattimer, Kelcie L. Hubach, Jennifer A. Case, Junyi Yang, Casey G. Weber, Julie A. Louk, Devin J. Rose, Gayaneh Kyureghian, Daniel A. Peterson, Mark D. Haub, Jens Walter

Food for Health: Publications

The involvement of the gut microbiota in metabolic disorders, and the ability of whole grains to affect both host metabolism and gut microbial ecology, suggest that some benefits of whole grains are mediated through their effects on the gut microbiome. Nutritional studies that assess the effect of whole grains on both the gut microbiome and human physiology are needed. We conducted a randomized cross-over trial with four-week treatments in which 28 healthy humans consumed a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB), and characterized their impact on …

Microbial Co-Occurrence Relationships In The Human Microbiome, Karoline Faust, J. Fah Sathirapongsasuti, Jacques Izard, Dirk Gevers, Jeroen Raes, Curtis Huttenhower

Department of Food Science and Technology: Faculty Publications

The healthy microbiota show remarkable variability within and among individuals. In addition to external exposures, ecological relationships (both oppositional and symbiotic) between microbial inhabitants are important contributors to this variation. It is thus of interest to assess what relationships might exist among microbes and determine their underlying reasons. The initial Human Microbiome Project (HMP) cohort, comprising 239 individuals and 18 different microbial habitats, provides an unprecedented resource to detect, catalog, and analyze such relationships. Here, we applied an ensemble method based on multiple similarity measures in combination with generalized boosted linear models (GBLMs) to taxonomic marker (16S rRNA gene) profiles …

Structure, Function And Diversity Of The Healthy Human Microbiome, Curtis Huttenhower, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. …

Metabolic Reconstruction For Metagenomic Data And Its Application To The Human Microbiome, Sahar Abubucker, Nicola Segata, Johannes Goll, Alyxandria M. Schubert, Jacques Izard, Brandi L. Cantarel, Beltran Rodriguez-Mueller, Jeremy Zucker, Mathangi Thiagarajan, Bernard Henrissat, Owen White, Scott T. Scott, Barbara Methé, Patrick D. Schloss, Dirk Gever, Makedonka Mitreva, Curtis Huttenhower

Department of Food Science and Technology: Faculty Publications

Microbial communities carry out the majority of the biochemical activity on the planet, and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome. Shotgun sequencing of such communities’ metagenomes provides information complementary to organismal abundances from taxonomic markers, but the resulting data typically comprise short reads from hundreds of different organisms and are at best challenging to assemble comparably to single-organism genomes. Here, we describe an alternative approach to infer the functional and metabolic potential of a microbial community metagenome. We determined the gene families and pathways present or absent within a community, as …

Composition Of The Adult Digestive Tract Bacterial Microbiome Based On Seven Mouth Surfaces, Tonsils, Throat And Stool Samples, Nicola Segata, Susan Kinder Haake, Peter Mannon, Katherine P. Lemon, Levi Waldron, Dirk Gevers, Curtis Huttenhower, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Background: To understand the relationship between our bacterial microbiome and health, it is essential to define the microbiome in the absence of disease. The digestive tract includes diverse habitats and hosts the human body’s greatest bacterial density. We describe the bacterial community composition of ten digestive tract sites from more than 200 normal adults enrolled in the Human Microbiome Project, and metagenomically determined metabolic potentials of four representative sites.

Results: The microbiota of these diverse habitats formed four groups based on similar community compositions: buccal mucosa, keratinized gingiva, hard palate; saliva, tongue, tonsils, throat; sub- and supra-gingival plaques; …

Single-Chain Vαvβ T Cell Receptors Function Without Mispairing With Endogenous Tcr Chains1, David H. Aggen, Adam S. Chervin, Thomas M. Schmitt, Boris Engels, Jennifer D. Stone, Sarah A. Richman, Kurt H. Piepenbrink, Brian M. Baker, Philip D. Greenberg, Hans Schreiber, David M. Kranz

Food for Health: Publications

Transduction of exogenous T cell receptor (TCR) genes into patients’ activated peripheral blood T cells is a potent strategy to generate large numbers of specific T cells for adoptive therapy of cancer and viral diseases. However, the remarkable clinical promise of this powerful approach is still being overshadowed by a serious potential consequence: mispairing of the exogenous TCR chains with endogenous TCR chains. These “mixed” heterodimers can generate new specificities that result in graft-versus-host reactions. Engineering TCR constant regions of the exogenous chains with a cysteine promotes proper pairing and reduces the mispairing, but, as we show here, does not …

Conformational Melding Permits A Conserved Binding Geometry In Tcr Recognition Of Foreign And Self Molecular Mimics, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian M. Baker

Food for Health: Publications

Molecular mimicry between foreign and self antigens is a mechanism of T cell receptor cross reactivity and is thought to contribute to the development of autoimmunity. The αβ TCR A6 recognizes the foreign antigen Tax from the virus HTLV-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease HAM/TSP, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found here that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics, and that in contrast with other recent structures …

Coxsackievirus B3 Infection Leads To The Generation Of Cardiac Myosin Heavy Chain-Α-Reactive Cd4 T Cells In A/J Mice, Arunakumar Gangaplara, Chandirasegaran Massilamany, Deborah M. Brown, Gustavo A. Delhon, Asit K. Pattnaik, Nora Chapman, Noel Rose, David J. Steffen, Jay Reddy

Jay Reddy Publications

Enteroviruses like coxsackievirus B3 (CVB3) are common suspects in myocarditis/dilated cardiomyopathy patients. Autoimmunity has been proposed as an underlying mechanism, but direct evidence of its role is lacking. To delineate autoimmune response in CVB3 myocarditis, we used IA^k dextramers for cardiac myosin heavy chain (Myhc)-α 334–352. We have demonstrated that myocarditis-susceptible A/J mice infected with CVB3 generate Myhc-α-reactive CD4 T cells and such a repertoire was absent in naïve mice as measured by proliferative response to Myhc-α 334–352 and IA^k dextramer staining. We also detected Myhc-α 334–352 dextramer⁺ cells in the hearts of CVB3-infected mice. The autoreactive …

Disparate Degrees Of Hypervariable Loop Flexibility Control T Cell Receptor Cross-Reactivity, Specificity, And Binding Mechanism, Daniel R. Scott, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Steven A. Corcelli, Brian M. Baker

Food for Health: Publications

αβ T cell receptors recognize multiple antigenic peptides bound and presented by major histocompatibility complex molecules. TCR cross-reactivity has been attributed in part to flexibility of the complementarity-determining region loops, yet there have been limited direct studies of loop dynamics to determine the extent of its role. Here we studied the flexibility of the binding loops of the αβ TCR A6 utilizing crystallographic, spectroscopic, and computational methods. A significant role for flexibility in binding and cross-reactivity was indicated only for the CDR3α and CDR3β hypervariable loops. Examination of the energy landscapes of these two loops indicated that CDR3β possesses a …

Metagenomic Biomarker Discovery And Explanation, Nicola Segata, Jacques Izard, Levi Waldron, Dirk Gevers, Larisa Miropolsky, Wendy S. Garrett, Curtis Huttenhower

Department of Food Science and Technology: Faculty Publications

This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.

Includes supplemental materials.

Identification And Engineering Of Human Variable Regions That Allow Expression Of Stable Single-Chain T Cell Receptors, David H. Aggen, Adam S. Chervin, Francis K. Insaidoo, Kurt H. Piepenbrink, Brian M. Baker, David M. Kranz

Food for Health: Publications

Single-chain antibody fragments (scFv), consisting of two linked variable regions (V_H and V_L), are a versatile format for engineering and as potential antigen-specific therapeutics. Although the analogous format for T cell receptors (TCRs), consisting of two linked V regions (Vα and Vβ; referred to here as scTv), could provide similar opportunities, all wild-type scTv proteins examined to date are unstable. This obstacle has prevented scTv fragments from being widely used for engineering or therapeutics. To further explore whether some stable human scTv fragments could be expressed, we used a yeast system in which display of properly folded …

Fluorine Substitutions In An Antigenic Peptide Selectively Modulate T Cell Receptor Binding In A Minimally Perturbing Manner, Kurt H. Piepenbrink, Oleg Y. Borbulevych, Ruth F. Sommese, John Clemens, Kathrynq M. Armstrong, Clare Desmond, Priscilla Do, Brian M. Baker

Food for Health: Publications

T cell receptor (TCR) recognition of antigenic peptides bound and presented by major histocompatibility complex (MHC) molecules forms the basis of the cellular immune response to pathogens and cancer. TCRs bind peptide/MHC molecules weakly and with fast kinetics, features which have hindered detailed biophysical studies of these interactions. Modified peptides resulting in enhanced TCR binding could help overcome these challenges. Further, there is considerable interest in using modified peptides with enhanced TCR binding as the basis for clinical vaccines. Here, we studied how fluorine substitutions in an antigenic peptide can selectively impact TCR recognition. Using a structure-guided design approach, we …

Identification Of A Second Mimicry Epitope From Acanthamoeba Castellanii That Induces Cns Autoimmunity By Generating Cross-Reactive T Cells For Mbp 89–101 In Sjl Mice, Chandirasegaran Massilamany, Oluwatoyin A. Asojo, Arunakumar Gangaplara, David J. Steffen, Jay Reddy

Jay Reddy Publications

We had previously reported that Acanthamoeba castellanii (ACA) contains a mimicry epitope for proteolipid protein 139–151 capable of inducing central nervous system (CNS) autoimmunity in SJL/J mice. We now present evidence that ACA also contains a mimicry epitope for myelin basic protein (MBP) 89–101, a derivative from amoebic nicotinamide adenine dinucleotide dehydrogenase subunit 2 (NAD). The epitope, NAD 108–120, contains a discontinuous stretch of six amino acids in the core region (VVFFKNIILIGFL) sharing 46% identity with MBP 89–101 (VHFFKNIVTPRTP; identical residues are underlined). SJL mice immunized with NAD 108–120 develop encephalomyelitis similar to the disease induced by the cognate peptide. …

The Human Oral Microbiome, Floyd E. Dewhirst, Tuste Chen, Jacques Izard, Bruce J. Paster, Anne C. R. Tanner, Wen-Han Yu, Abirami Lakshmanan, William G. Wade

Department of Food Science and Technology: Faculty Publications

The human oral cavity contains a number of different habitats, including the teeth, gingival sulcus, tongue, cheeks, hard and soft palates, and tonsils, which are colonized by bacteria. The oral microbiome comprises over 600 prevalent taxa at the species level, with distinct subsets predominating at different habitats. The oral microbiome has been extensively characterized by cultivation and culture-independent molecular methods such as 16S rRNA cloning. Unfortunately, the vast majority of unnamed oral taxa are referenced by clone numbers or 16S rRNA GenBank accession numbers, often without taxonomic anchors. The first aim of this research was to collect 16S rRNA gene …

T Cell Receptor Cross-Reactivity Directed By Antigen-Dependent Tuning Of Peptide-Mhc Molecular Flexibility, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian E. Gloor, Daniel R. Scott, Ruth F. Sommese, David K. Cole, Andrew K. Sewell, Brian M. Baker

Food for Health: Publications

Tell mediated immunity requires T cell receptor (TCR) cross-reactivity, the mechanisms behind which remain incompletely elucidated. The αβ TCR A6 recognizes both the Tax (LLFGYPVYV) and Tel1p (MLWGYLQYV) peptides presented by the human class I MHC molecule HLA-A2. Here we found that although the two ligands are ideal structural mimics, they form substantially different interfaces with A6, with conformational differences in the peptide, the TCR, and unexpectedly, the MHC molecule. The differences between the Tax and Tel1p ternary complexes could not be predicted from the free peptide-MHC structures and are inconsistent with a traditional induced-fit mechanism. Instead, the differences were …

Killing Of Treponema Denticola By Mouse Peritoneal Macrophages, P. Gaibani, C. Vocale, S. Ambretti, F. Cavrini, Jacques Izard, L. Miragliotta, M. T. Pellegrino, V. Sambri

Department of Food Science and Technology: Faculty Publications

Treponema denticola has been identified as an important cause of periodontal disease and hypothesized to be involved in extra-oral infections. The objective of this study was to investigate the role of T. denticola cell length and motility during mouse peritoneal macrophages in vitro uptake. Macrophages, incubated under aerobic and anaerobic conditions, produced a similar amount of TNF-α when stimulated with Escherichia coli LPS. The uptake of FlgE- and CfpA-deficient mutants of T. denticola was significantly increased compared with the wild-type strain, due to cell size or lack of motility. Opsonization with specific antibodies considerably improved the treponemes’ uptake. …

Native Cellular Architecture Of Treponema Denticola Revealed By Cryo-Electron Tomography, Jacques Izard, Chyong-Ere Hsieh, Ronald J. Limberger, Carmen A. Mannella, Michael Marko

Department of Food Science and Technology: Faculty Publications

Using cryo-electron tomography, we are developing a refined description of native cellular structures in the pathogenic spirochete Treponema denticola. Tightly organized bundles of periplasmic flagella were readily observed in intact plunge-frozen cells. The periplasmic space was measured in both wild-type and aflagellate strains, and found to widen by less than the diameter of flagella when the latter are present. This suggests that a structural change occurs in the peptidoglycan layer to accommodate the presence of the flagella. In dividing cells, the flagellar filaments were found to bridge the cytoplasmic cylinder constriction site. Cytoplasmic filaments, adjacent to the inner membrane, …

Pyramidobacter Piscolens Gen. Nov., Sp. Nov., A Member Of The Phylum ‘Synergistetes’ Isolated From The Human Oral Cavity, Julia Downes, Sonia R. Vartoukian, Floyd E. Dewhirst, Jacques Izard, Tsute Chen, Wen-Han Yu, Iain C. Sutcliffe, William G. Wade

Department of Food Science and Technology: Faculty Publications

Four strains of anaerobic, gram-negative bacilli isolated from the human oral cavity were subjected to a comprehensive range of phenotypic and genotypic tests and were found to comprise a homogeneous group distinct from any species with validly published names. 16S rRNA and 23S rRNA gene sequence analyses and DNA–DNA reassociation data revealed that the strains constituted a novel group within the phylum ‘Synergistetes’ and were most closely related to Jonquetella anthropi. Two libraries of randomly cloned DNA were prepared from strain W5455T and were sequenced to provide a genome survey as a resource for metagenomic studies. A new genus …

Cryo-Electron Tomography Elucidates The Molecular Architecture Of Treponema Pallidum, The Syphilis Spirochete, Jacques Izard, Christian Renken, Chyong-Ere Hsieh, Daniel C. Desrosiers, Star Dunham-Ems, Carson La Vake, Linda L. Gebhardt, Ronald J. Limberger, David L. Cox, Michael Marko, Justin D. Radolf

Department of Food Science and Technology: Faculty Publications

Cryo-electron tomography (CET) was used to examine the native cellular organization of Treponema pallidum, the syphilis spirochete. T. pallidum cells appeared to form flat waves, did not contain an outer coat and, except for bulges over the basal bodies and widening in the vicinity of flagellar filaments, displayed a uniform periplasmic space. Although the outer membrane (OM) generally was smooth in contour, OM extrusions and blebs frequently were observed, highlighting the structure’s fluidity and lack of attachment to underlying periplasmic constituents. Cytoplasmic filaments converged from their attachment points opposite the basal bodies to form arrays that ran roughly …

Distinct Functions Of Autoreactive Memory And Effector Cd4+ T Cells In Experimental Autoimmune Encephalomyelitis, Wassim Elyaman, Pia Kivisäkk, Jay Reddy, Tanuja Chitnis, Khadir Raddassi, Jaime Imitola, Elizabeth Bradshaw, Vijay K. Kuchroo, Hideo Yagita, Mohamed H. Sayegh, Samia J. Khoury

Jay Reddy Publications

The persistence of human autoimmune diseases is thought to be mediated predominantly by memory T cells. We investigated the phenotype and migration of memory versus effector T cells in vivo in experimental autoimmune encephalomyelitis (EAE). We found that memory CD4⁺ T cells up-regulated the activation marker CD44 as well as CXCR3 and ICOS, proliferated more and produced more interferon-γ and less interleukin-17 compared to effector T cells. Moreover, adoptive transfer of memory T cells into T cell receptor (TCR)αβ^-/- recipients induced more severe disease than did effector CD4⁺ T cells with marked central nervous system inflammation and …

Conformational Changes And Flexibility In T-Cell Receptor Recognition Of Peptide–Mhc Complexes, Kathryn M. Armstrong, Kurt H. Piepenbrink, Brian M. Baker

Food for Health: Publications

A necessary feature of the immune system, TCR (T-cell receptor) cross-reactivity has been implicated in numerous autoimmune pathologies and is an underlying cause of transplant rejection. Early studies of the interactions of αβ TCRs (T-cell receptors) with their peptide–MHC ligands suggested that conformational plasticity in the TCR CDR (complementarity determining region) loops is a dominant contributor to T-cell cross-reactivity. Since these initial studies, the database of TCRs whose structures have been solved both bound and free is now large enough to permit general conclusions to be drawn about the extent of TCR plasticity and the types and locations of motion …

Modulation Of Cd4 Co-Receptor Limits Spontaneous Autoimmunity When High-Affinity Transgenic Tcr Specific For Self-Antigen Is Expressed On A Genetically Resistant Background, Zsolt Illés, Hanspeter Waldner, Jay Reddy, Ana C. Anderson, Raymond A. Sobel, Vijay K. Kuchroo

Jay Reddy Publications

Myelin proteolipid protein (PLP) 139–151 is an immunodominant peptide that induces experimental autoimmune encephalomyelitis (EAE) in H-2^s SJL/J mice. While PLP 139–151-specific TCR transgenic (tg) 4E3 mice develop fulminant spontaneous disease on the susceptible SJL/J background, spontaneous EAE is dramatically reduced on the H-2^s congenic B10.S background. On this resistant background, we observed a high frequency of positively selected tg CD42CD82 (DN) thymocytes and peripheral DN tg T cells. Splenic DN tg T cells responded to anti-CD3 stimulation similarly to CD41 cells, but proliferative and cytokine responses to PLP 139–151 were blunted, implying that CD4 coreceptor down-regulation modulated …

Genetic Microheterogeneity And Phenotypic Variation Of Helicobacter Pylori Arginase In Clinical Isolates, Justin Hovey, Emily Watson, Melanie Langford, Ellen Hildebrandt, Sangeetha Bathala, Jeffrey Bolland, Domenico Spadafora, George Mendz, David Mcgee

School of Biological Sciences: Faculty Publications

Background: Clinical isolates of the gastric pathogen Helicobacter pylori display a high level of genetic macro- and microheterogeneity, featuring a panmictic, rather than clonal structure. The ability of H. pylori to survive the stomach acid is due, in part, to the arginase-urease enzyme system. Arginase (RocF) hydrolyzes L-arginine to L-ornithine and urea, and urease hydrolyzes urea to carbon dioxide and ammonium, which can neutralize acid.

Results: The degree of variation in arginase was explored at the DNA sequence, enzyme activity and protein expression levels. To this end, arginase activity was measured from 73 minimally-passaged clinical isolates and six laboratory-adapted strains …

Treponema Denticola In Disseminating Endodontic Infections, F. Foschi, Jacques Izard, H. Sasaki, V. Sambri, C. Prati, R. Müller, P. Stashenko

Department of Food Science and Technology: Faculty Publications

Treponema denticola is a consensus periodontal pathogen that has recently been associated with endodontic pathology. In this study, the effect of mono-infection of the dental pulp with T. denticola and with polymicrobial “red-complex” organisms (RC) (Porphyromonas gingivalis, Tannerella forsythia, and T. denticola) in inducing disseminating infections in wild-type (WT) and severe-combined-immunodeficiency (SCID) mice was analyzed. After 21 days, a high incidence (5/10) of orofacial abscesses was observed in SCID mice mono-infected with T. denticola, whereas abscesses were rare in SCID mice infected with the red-complex organisms or in wild-type mice. Splenomegaly was …

Monoclonal Antibodies To Distinct Regions Of Human Myelin Proteolipid Protein Simultaneously Recognize Central Nervous System Myelin And Neurons Of Many Vertebrate Species, Edward A. Greenfield, Jay Reddy, Andrew Lees, Charissa A. Dyer, Omanand Koul, Khuong Nguyen, Shannon Bell, Nasim Kassam, Julian Hinojoza, Mary Jane Eaton, Marjorie B. Lees, Vijay K. Kuchroo, Raymond A. Sobel

Jay Reddy Publications

Myelin proteolipid protein (PLP), the major protein of mammalian CNS myelin, is a member of the proteolipid gene family (pgf). It is an evolutionarily conserved polytopic integral membrane protein and a potential autoantigen in multiple sclerosis (MS). To analyze antibody recognition of PLP epitopes in situ, monoclonal antibodies (mAbs) specific for different regions of human PLP (50–69, 100–123, 139–151, 178–191, 200–219, 264–276) were generated and used to immunostain CNS tissues of representative vertebrates. mAbs to each region recognized whole human PLP on Western blots; the anti-100–123 mAb did not recognize DM-20, the PLP isoform that lacks residues 116–150. All of …

Or.76. Myelin Specific Regulatory T-Cells Expand From Naturally Occurring Regulatory T-Cells And Accumulate In The Cns During Eae [Abstract Only], Thomas Korn, Jay Reddy, Wenda Gao, Terry Strom, Mohamed Oukka, Vijay K. Kuchroo

Jay Reddy Publications

FoxP3 is a lineage specific marker for regulatory T-cells (Treg). We have generated FoxP3 knock-in (KI) mice by introducing a bicistronic GFP reporter into the endogenous FoxP3 locus, allowing us to faithfully track T-reg in vivo. Recently, we have also generated a MOG 35-55/IAb-tetramer. The combination of these two technologies enables us to study the in vivo behavior of myelin specific T-reg and effector T-cells (T-eff) during EAE. Upon immunization with MOG 35-55, we identified a population of MOG-tetramerreactive T-reg in the peripheral lymphoid compartment. T-reg trafficked to the CNS where they were readily detected as early as day 10 …

Or.107. Tim-1 Plays A Crucial Role In The Expansion Of Autopathogneic T-Cells And Regulation Of Autoimmunity [Abstract Only], Sheng Xioa, Nader Najafian, Jay Reddy, Monica Albin, Chen Zhu, Ana Anderson, Zheng Zhang, Cristina Gutierrez, Raymond Sobel, Dale Umetsu, Hideo Yagita, Hisaya Akiba, Mohamed Sayegh, Rosemarie Dekruyff, Vijay K. Kuchroo

Jay Reddy Publications

T-cell immunoglobulin and mucin (TIM) family Members are differentially expressed on Th1 and Th2 cells. Polymorphisms of TIM-1 have been associated with susceptibility to asthma; however, its role in regulating autoimmunity has not been studied. Here, we have used an agonistic antiTIM-1 antibody (Ab, Clone 3B3) which has previously been shown to costimulate T-cell activation and expansion, to analyze the role of TIM-1 in the development and regulation of experimental autoimmune encephalomyelitis (EAE). Treatment with 3B3 dramatically enhances the severity of EAE as well as the frequency of encephalitogenic CD4+ T-cells and the production of IFN-g and IL-17 by these …

Tannerella Forsythia, A Periodontal Pathogen Entering The Genomic Era, Anne C. R. Tanner, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Several questions need to be addressed to evaluate whether Tannerella forsythia is to be considered a periodontal pathogen. T. forsythia has been detected in periodontal health and disease, so could it be a pathogen? The species was not detected in many studies despite finding other putative pathogens, so could it be important in pathogenicity? The challenges of working with T. forsythia include its fastidious and anaerobic growth requirements for cultural detection. Thus, studies associating T. forsythia with periodontal and other oral infections have used noncultural approaches (immunoassays and DNA-based assays) in addition to cultural approaches. We feel …