Medical Immunology Commons^™

The Final (Oral Ebola) Vaccine Trial On Captive Chimpanzees?, Peter D. Walsh, Drishya Kurup, Dana L. Hasselschwert, Christoph Wirblich, Jason E. Goetzmann, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? We used captive chimpanzees to test oral delivery of a rabies virus (RABV) vectored vaccine against Ebola virus (EBOV), a major threat to wild chimpanzees and gorillas. EBOV GP and RABV GP-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. Chimpanzee sera also showed robust neutralizing activity against RABV and pseudo-typed EBOV. Vaccination did not induce serious health complications. Blood chemistry, hematologic, and body mass correlates of psychological stress suggested …

Influence Of Sex/Gender And Race On Responses To Raltegravir Combined With Tenofovir-Emtricitabine In Treatment-Naive Human Immunodeficiency Virus-1 Infected Patients: Pooled Analyses Of The Startmrk And Qdmrk Studies., Kathleen E. Squires, Linda-Gail Bekker, Christine Katlama, Yazdan Yazdanpanah, Yan Zhou, Anthony J Rodgers, Mark J Dinubile, Peter A Sklar, Randi Y Leavitt, Hedy Teppler

Department of Medicine Faculty Papers

BACKGROUND: Antiretroviral therapy in human immunodeficiency virus (HIV)-infected women and blacks merits particular scrutiny because these groups have been underrepresented in clinical trials.

METHODS: To document the effects of raltegravir across sex and racial lines, we conducted a pooled subgroup analysis of the efficacy and safety of raltegravir 400 mg BID plus tenofovir-emtricitabine by sex (women vs men) and self-identified race (black vs non-black) using phase 3 studies in treatment-naive patients.

RESULTS: Study participants included 42 black women, 102 non-black women, 48 black men, and 477 non-black men. Clade B infections were less common in women (43.8%) than men (84.6%) …

T Cell Migration From Inflamed Skin To Draining Lymph Nodes Requires Intralymphatic Crawling Supported By Icam-1/Lfa-1 Interactions., Alvaro Teijeira, Morgan C. Hunter, Erica Russo, Steven T Proulx, Thomas Frei, Gudrun F. Debes, Marc Coles, Ignacio Melero, Michael Detmar, Ana Rouzaut, Cornelia Halin

Department of Microbiology and Immunology Faculty Papers

T cells are the most abundant cell type found in afferent lymph, but their migration through lymphatic vessels (LVs) remains poorly understood. Performing intravital microscopy in the murine skin, we imaged T cell migration through afferent LVs in vivo. T cells entered into and actively migrated within lymphatic capillaries but were passively transported in contractile collecting vessels. Intralymphatic T cell number and motility were increased during contact-hypersensitivity-induced inflammation and dependent on ICAM-1/LFA-1 interactions. In vitro, blockade of endothelial cell-expressed ICAM-1 reduced T cell adhesion, crawling, and transmigration across lymphatic endothelium and decreased T cell advancement from capillaries into lymphatic collectors …

Applying Multiple Data Collection Tools To Quantify Human Papillomavirus Vaccine Communication On Twitter., Philip M. Massey, Amy Leader, Elad Yom-Tov, Alexandra Budenz, Kara Fisher, Ann C. Klassen

Department of Medical Oncology Faculty Papers

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. There are several vaccines that protect against strains of HPV most associated with cervical and other cancers. Thus, HPV vaccination has become an important component of adolescent preventive health care. As media evolves, more information about HPV vaccination is shifting to social media platforms such as Twitter. Health information consumed on social media may be especially influential for segments of society such as younger populations, as well as ethnic and racial minorities.

OBJECTIVE: The objectives of our study were to quantify HPV vaccine communication on …

Evaluating Frequency And Quality Of Pathogen-Specific T Cells., Nadia Anikeeva, Dolores Grosso, Yuri Sykulev

Department of Microbiology and Immunology Faculty Papers

It is generally accepted that enumeration and characterization of antigen-specific T cells provide essential information about potency of the immune response. Here, we report a new technique to determine the frequency and potency of antigen-specific CD8 T cells. The assay measures changes of intracellular Ca(2+) in real time by fluorescent microscopy in individual CD8 T cells responding to cognate peptides. The T cells form continuous monolayer, enabling the cells to present the peptides to each other. This approach allows us to evaluate the kinetics of intracellular Ca(2+) signalling that characterizes the quality of T cell response. We demonstrate the usefulness …

Kinase-Independent Function Of Rip1, Critical For Mature T-Cell Survival And Proliferation., John Bertin, Peter J. Gough, Jianke Zhang, John P. Dowling, Yubo Cai

Department of Microbiology and Immunology Faculty Papers

The death receptor, Fas, triggers apoptotic death and is essential for maintaining homeostasis in the peripheral lymphoid organs. RIP1 was originally cloned when searching for Fas-binding proteins and was later shown to associate also with the signaling complex of TNFR1. Although Fas exclusively induces apoptosis, TNFR1 primarily activates the pro-survival/pro-inflammatory NF-κB pathway. Mutations in Fas lead to lymphoproliferative (lpr) diseases, and deletion of TNFR1 results in defective innate immune responses. However, the function of RIP1 in the adult lymphoid system has not been well understood, primarily owing to perinatal lethality in mice lacking the entire RIP1 protein in germ cells. …

The Immunomodulatory Role Of Adjuvants In Vaccines Formulated With The Recombinant Antigens Ov-103 And Ov-Ral-2 Against Onchocerca Volvulus In Mice., Jessica A. Hess Ligas, Bin Zhan, April R. Torigian, John B. Patton, Nikolai Petrovsky, Tingting Zhan, Maria Elena Bottazzi, Peter J. Hotez, Thomas R. Klei, Sara Lustigman, David Abraham

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types …

Hiv-1 Genetic Variation Resulting In The Development Of New Quasispecies Continues To Be Encountered In The Peripheral Blood Of Well-Suppressed Patients., Will Dampier, Michael R Nonnemacher, Joshua Mell, Joshua Earl, Garth D Ehrlich, Vanessa Pirrone, Benjamas Aiamkitsumrit, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Jeffrey M Jacobson, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

As a result of antiretroviral therapeutic strategies, human immunodeficiency virus type 1 (HIV-1) infection has become a long-term clinically manageable chronic disease for many infected individuals. However, despite this progress in therapeutic control, including undetectable viral loads and CD4+ T-cell counts in the normal range, viral mutations continue to accumulate in the peripheral blood compartment over time, indicating either low level reactivation and/or replication. Using patients from the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort, whom have been sampled longitudinally for more than 7 years, genetic change was modeled against to the dominant integrated proviral quasispecies with …

Ifn-Γ Receptor And Stat1 Signaling In B Cells Are Central To Spontaneous Germinal Center Formation And Autoimmunity., Phillip P. Domeier, Sathi Babu Chodisetti, Chetna Soni, Stephanie L. Schell, Melinda J. Elias, Eric B. Wong, Timothy K. Cooper, Daisuke Kitamura, Ziaur S.M. Rahman

Department of Microbiology and Immunology Faculty Papers

Spontaneously developed germinal centers (GCs [Spt-GCs]) harbor autoreactive B cells that generate somatically mutated and class-switched pathogenic autoantibodies (auto-Abs) to promote autoimmunity. However, the mechanisms that regulate Spt-GC development are not clear. In this study, we report that B cell-intrinsic IFN-γ receptor (IFN-γR) and STAT1 signaling are required for Spt-GC and follicular T helper cell (Tfh cell) development. We further demonstrate that IFN-γR and STAT1 signaling control Spt-GC and Tfh cell formation by driving T-bet expression and IFN-γ production by B cells. Global or B cell-specific IFN-γR deficiency in autoimmune B6.Sle1b mice leads to significantly reduced Spt-GC and Tfh cell …

Vaccination Of Gerbils With Bm-103 And Bm-Ral-2 Concurrently Or As A Fusion Protein Confers Consistent And Improved Protection Against Brugia Malayi Infection., Sridhar Arumugam, Junfei Wei, Zhuyun Liu, David Abraham, Aaron Bell, Maria Elena Bottazzi, Peter J Hotez, Bin Zhan, Sara Lustigman, Thomas R Klei

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The Brugia malayi Bm-103 and Bm-RAL-2 proteins are orthologous to Onchocerca volvulus Ov-103 and Ov-RAL-2, and which were selected as the best candidates for the development of an O. volvulus vaccine. The B. malayi gerbil model was used to confirm the efficacy of these Ov vaccine candidates on adult worms and to determine whether their combination is more efficacious.

METHODOLOGY AND PRINCIPLE FINDINGS: Vaccine efficacy of recombinant Bm-103 and Bm-RAL-2 administered individually, concurrently or as a fusion protein were tested in gerbils using alum as adjuvant. Vaccination with Bm-103 resulted in worm reductions of 39%, 34% and 22% on …

Murine Cmv Infection Induces The Continuous Production Of Mucosal Resident T Cells., Corinne J Smith, Sofia Caldeira-Dantas, Holly Turula, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Cytomegalovirus (CMV) is a herpesvirus that persists for life and maintains extremely large numbers of T cells with select specificities in circulation. However, it is unknown how viral persistence impacts T cell populations in mucosal sites. We found that many murine (M)CMV-specific CD8s in mucosal tissues became resident memory T cells (TRM). These cells adopted an intraepithelial localization in the salivary gland that correlated with, but did not depend on, expression of the integrin CD103. MCMV-specific TRM cells formed early after infection, and spleen-localized cells had reduced capacities to become TRM at late times. Surprisingly, however, small numbers of new …

Human Polyclonal Antibodies Produced Through Dna Vaccination Of Transchromosomal Cattle Provide Mice With Post-Exposure Protection Against Lethal Zaire And Sudan Ebolaviruses., Callie E Bounds, Steven A Kwilas, Ana I Kuehne, Jennifer M Brannan, Russell R Bakken, John M Dye, Jay W Hooper, Lesley C Dupuy, Barry Ellefsen, Drew Hannaman, Hua Wu, Jin-An Jiao, Eddie J Sullivan, Connie S Schmaljohn, Matthias J. Schnell

Department of Medicine Faculty Papers

DNA vaccination of transchromosomal bovines (TcBs) with DNA vaccines expressing the codon-optimized (co) glycoprotein (GP) genes of Ebola virus (EBOV) and Sudan virus (SUDV) produce fully human polyclonal antibodies (pAbs) that recognize both viruses and demonstrate robust neutralizing activity. Each TcB was vaccinated by intramuscular electroporation (IM-EP) a total of four times and at each administration received 10 mg of the EBOV-GPco DNA vaccine and 10 mg of the SUDV-GPco DNA vaccine at two sites on the left and right sides, respectively. After two vaccinations, robust antibody responses (titers > 1000) were detected by ELISA against whole irradiated EBOV or SUDV …

Mechanisms Of Immunological Tolerance In Central Nervous System Inflammatory Demyelination., Elisabeth R. Mari, Jason N. Moore, Guang-Xian Zhang, A. M. Rostami

Department of Neurology Faculty Papers

Multiple sclerosis is a complex autoimmune disease of the central nervous system that results in a disruption of the balance between pro-inflammatory and anti-inflammatory signals in the immune system. Given that central nervous system inflammation can be suppressed by various immunological tolerance mechanisms, immune tolerance has become a focus of research in the attempt to induce long-lasting immune suppression of pathogenic T cells. Mechanisms underlying this tolerance induction include induction of regulatory T cell populations, anergy and the induction of tolerogenic antigen-presenting cells. The intravenous administration of encephalitogenic peptides has been shown to suppress experimental autoimmune encephalomyelitis and induce tolerance …

Immune Reconstitution But Persistent Activation After 48 Weeks Of Antiretroviral Therapy In Youth With Pre-Therapy Cd4 >350 In Atn 061., Bret J. Rudy, Bill G. Kapogiannis, Carol Worrell, Kathleen E. Squires, James Bethel, Su Li, Craig M. Wilson, Allison Agwu, Patricia Emmanuel, Georgine Price, Stephanie Hudey, Maureen M. Goodenow, John W. Sleasman

Department of Medicine Faculty Papers

BACKGROUND: Measures of immune outcomes in youth who initiate combination antiretroviral therapy (cART) early in HIV infection are limited.

DESIGN: Adolescent Trials Network 061 examined changes over 48 weeks of cART in T-cell subsets and markers of T-cell and macrophage activation in subjects with pre-therapy CD4 > 350 cells/mm. All subjects had optimal viral suppression from weeks 24 through 48.

METHODS: Subjects (n = 48) initiated cART with tenofovir/emtricitabine plus ritonavir-boosted atazanavir. Data were collected at baseline and weeks 12, 24, and 48. Trends were compared to uninfected controls.

RESULTS: Significant increases over 48 weeks were noted in all CD4 populations, …

Reverse Genetics Of Mononegavirales: How They Work, New Vaccines, And New Cancer Therapeutics., Christian K Pfaller, Roberto Cattaneo, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

The order Mononegavirales includes five families: Bornaviridae, Filoviridae, Nyamaviridae, Paramyxoviridae, and Rhabdoviridae. The genome of these viruses is one molecule of negative-sense single strand RNA coding for five to ten genes in a conserved order. The RNA is not infectious until packaged by the nucleocapsid protein and transcribed by the polymerase and co-factors. Reverse genetics approaches have answered fundamental questions about the biology of Mononegavirales. The lack of icosahedral symmetry and modular organization in the genome of these viruses has facilitated engineering of viruses expressing fluorescent proteins, and these fluorescent proteins have provided important insights about the molecular and cellular …

The Onchocerciasis Vaccine For Africa-Tova-Initiative., Peter J Hotez, Maria Elena Bottazzi, Bin Zhan, Benjamin L Makepeace, Thomas R Klei, David Abraham, David W Taylor, Sara Lustigman

Department of Microbiology and Immunology Faculty Papers

No abstract provided.

Memory T Cells Specific For Murine Cytomegalovirus Re-Emerge After Multiple Challenges And Recapitulate Immunity In Various Adoptive Transfer Scenarios., Michael Quinn, Holly Turula, Mayank Tandon, Berthony Deslouches, Toktam Moghbeli, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Reconstitution of CMV-specific immunity after transplant remains a primary clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV-specific T cells can be an effective therapeutic approach. Because of viral persistence, most CMV-specific CD8(+) T cells become terminally differentiated effector phenotype CD8(+) T cells (TEFF). A minor subset retains a memory-like phenotype (memory phenotype CD8(+) T cells [TM]), but it is unknown whether these cells retain memory function or persist over time. Interestingly, recent studies suggest that CMV-specific CD8(+) T cells with different phenotypes have different abilities to reconstitute sustained immunity after transfer. The immunology of human CMV infections …

Impact Of Distinct Poxvirus Infections On The Specificities And Functionalities Of Cd4+ T Cell Responses., Nicholas A Siciliano, Adam R Hersperger, Aimee M Lacuanan, Ren-Huan Xu, John Sidney, Alessandro Sette, Luis J Sigal, Laurence C. Eisenlohr

Department of Microbiology and Immunology Faculty Papers

UNLABELLED: The factors that determine CD4+ T cell (TCD4+) specificities, functional capacity, and memory persistence in response to complex pathogens remain unclear. We explored these parameters in the C57BL/6 mouse through comparison of two highly related (>92% homology) poxviruses: ectromelia virus (ECTV), a natural mouse pathogen, and vaccinia virus (VACV), a heterologous virus that nevertheless elicits potent immune responses. In addition to elucidating several previously unidentified major histocompatibility complex class II (MHC-II)-restricted epitopes, we observed many qualitative and quantitative differences between the TCD4+ repertoires, including responses not elicited by VACV despite complete sequence conservation. In addition, we observed functional …

Vaccination With A Genetically Modified Brugia Malayi Cysteine Protease Inhibitor-2 Reduces Adult Parasite Numbers And Affects The Fertility Of Female Worms Following A Subcutaneous Challenge Of Mongolian Gerbils (Meriones Unguiculatus) With B. Malayi Infective Larvae., Sridhar Arumugam, Junfei Wei, Danielle Ward, David Abraham, Sara Lustigman, Bin Zhan, Thomas R. Klei

Department of Microbiology and Immunology Faculty Papers

Vaccination of Mongolian gerbils with Brugia malayi cysteine protease inhibitor-2 in which the amino acid Asn66 was mutated to Lys66 (Bm-CPI-2M) resulted in reduced parasite numbers of 48.6% and 48.0% at 42 and 90 days p.i. with B. malayi L3s. Fertility of female worms was also affected at 90 days p.i. In vitro killing of L3s observed in the presence of gerbil peritoneal exudate cells and anti-Bm-CPI-2M sera suggests antibody-dependent cell-mediated cytotoxicity as a putative protective mechanism. These observations suggest that Bm-CPI-2M is a promising prophylactic and anti-fecundity vaccine candidate.

Epithelial Immunization Induces Polyfunctional Cd8+ T Cells And Optimal Mousepox Protection., Adam R Hersperger, Nicholas A Siciliano, Brian C Dehaven, Adam E. Snook, Laurence C. Eisenlohr

Department of Microbiology and Immunology Faculty Papers

We assessed several routes of immunization with vaccinia virus (VACV) in protecting mice against ectromelia virus (ECTV). By a wide margin, skin scarification provided the greatest protection. Humoral immunity and resident-memory T cells notwithstanding, several approaches revealed that circulating, memory CD8(+) T cells primed via scarification were functionally superior and conferred enhanced virus control. Immunization via the epithelial route warrants further investigation, as it may also provide enhanced defense against other infectious agents.

Vaccines To Combat River Blindness: Expression, Selection And Formulation Of Vaccines Against Infection With Onchocerca Volvulus In A Mouse Model., Jessica A. Hess, Bin Zhan, Sandra Bonne-Annee, Jessica M. Deckman, Maria Elena Bottazzi, Peter J. Hotez, Thomas R R. Klei, Sara Lustigman, David Abraham

Department of Microbiology and Immunology Faculty Papers

Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation …

Systemic Hematogenous Maintenance Of Memory Inflation By Mcmv Infection., Corinne J Smith, Holly Turula, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Several low-grade persistent viral infections induce and sustain very large numbers of virus-specific effector T cells. This was first described as a response to cytomegalovirus (CMV), a herpesvirus that establishes a life-long persistent/latent infection, and sustains the largest known effector T cell populations in healthy people. These T cells remain functional and traffic systemically, which has led to the recent exploration of CMV as a persistent vaccine vector. However, the maintenance of this remarkable response is not understood. Current models propose that reservoirs of viral antigen and/or latently infected cells in lymph nodes stimulate T cell proliferation and effector differentiation, …

Extracellular Traps Are Associated With Human And Mouse Neutrophil And Macrophage Mediated Killing Of Larval Strongyloides Stercoralis., Sandra Bonne-Annee, Laura A. Kerepesi, Jessica A. Hess, Jordan Wesolowski, Fabienne Paumet, James B. Lok, Thomas J. Nolan, David Abraham

Department of Microbiology and Immunology Faculty Papers

Neutrophils are multifaceted cells that are often the immune system's first line of defense. Human and murine cells release extracellular DNA traps (ETs) in response to several pathogens and diseases. Neutrophil extracellular trap (NET) formation is crucial to trapping and killing extracellular pathogens. Aside from neutrophils, macrophages and eosinophils also release ETs. We hypothesized that ETs serve as a mechanism of ensnaring the large and highly motile helminth parasite Strongyloides stercoralis thereby providing a static target for the immune response. We demonstrated that S. stercoralis larvae trigger the release of ETs by human neutrophils and macrophages. Analysis of NETs revealed …

Cd27high/Klrg1low Cd8+ T Cells That Persist Throughout Mcmv Infection Are Highly Expansive And Have The Ability To Reestablish Mcmv Immunity, Michael Quinn, Holly Turula, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Abstract

Cytomegalovirus (CMV) is a herpesvirus that establishes life-long latency in 60-80% of Americans. Constant immune surveillance is necessary to prevent viral reactivation from latency and results in the accumulation of functional CMV-specific CD8+ T cells (CD8s) over time, a process termed memory inflation. As such, CMV reactivations remain a clinical concern for immunosuppressed patients and reconstituting CMV immunity is critical for the long-term prevention of CMV disease. Understanding the maintenance of memory inflation may reveal novel approaches to restore CMV immunity.

Previous work has shown that the majority of inflationary CD8s express a terminally-differentiated “effector” (T_EFF) phenotype, …

Characterization Of T-Bet And Eomes In Peripheral Human Immune Cells., James J. Knox, Gabriela L. Cosma, Michael R. Betts, Laura M. Mclane

Department of Microbiology and Immunology Faculty Papers

The T-box transcription factors T-bet and Eomesodermin (Eomes) have been well defined as key drivers of immune cell development and cytolytic function. While the majority of studies have defined the roles of these factors in the context of murine T-cells, recent results have revealed that T-bet, and possibly Eomes, are expressed in other immune cell subsets. To date, the expression patterns of these factors in subsets of human peripheral blood mononuclear cells beyond T-cells remain relatively uncharacterized. In this study, we used multiparametric flow cytometry to characterize T-bet and Eomes expression in major human blood cell subsets, including total CD4(+) …

Limited Brain Metabolism Changes Differentiate Between The Progression And Clearance Of Rabies Virus., Keith Schutsky, Carla Portocarrero, D Craig Hooper, Bernhard Dietzschold, Milosz Faber

Department of Microbiology and Immunology Faculty Papers

Central nervous system (CNS) metabolic profiles were examined from rabies virus (RABV)-infected mice that were either mock-treated or received post-exposure treatment (PET) with a single dose of the live recombinant RABV vaccine TriGAS. CNS tissue harvested from mock-treated mice at middle and late stage infection revealed numerous changes in energy metabolites, neurotransmitters and stress hormones that correlated with replication levels of viral RNA. Although the large majority of these metabolic changes were completely absent in the brains of TriGAS-treated mice most likely due to the strong reduction in virus spread, TriGAS treatment resulted in the up-regulation of the expression of …

Interleukin-7-Dependent B Lymphocytes Are Required For The Anti-Pneumococcal Polysaccharide Response And Protective Immunity To Streptococcus Pneumoniae, Gregory S. Dickinson, Phd, Raja Vuyyuru, Timothy L. Manser, Phd, John F. Kerney, Kishore Alugupalli, Phd

Department of Microbiology and Immunology Faculty Papers

Unlike human adults or adult mice, young children or young mice respond poorly to pneumococcal polysaccharides (PPS). In mice, B1b lymphocytes are the major responders to a variety of bacterial polysaccharides including PPS. Despite having B1b cells, young mice are severely impaired in responding to PPS, suggesting that B cells in the young are distinct from those in adults. Since B lymphopoeisis early in life is largely Interleukin-7 (IL-7)-independent, while in adults it is IL-7-dependent, we hypothesize that B cells developed in the presence of IL-7 are required for generating anti-PPS antibody responses. In support of this, we found that …

Myd88-Dependent Immunity To A Natural Model Of Vaccinia Virus Infection Does Not Involve Toll-Like Receptor 2., Michael L Davies, Janet J Sei, Nicholas A Siciliano, Ren-Huan Xu, Felicia Roscoe, Luis J Sigal, Laurence C. Eisenlohr, Christopher C Norbury

Department of Microbiology and Immunology Faculty Papers

UNLABELLED: Although the pattern recognition receptor Toll-like receptor 2 (TLR2) is typically thought to recognize bacterial components, it has been described to alter the induction of both innate and adaptive immunity to a number of viruses, including vaccinia virus (VACV). However, many pathogens that reportedly encode TLR2 agonists may actually be artifactually contaminated during preparation, possibly with cellular debris or merely with molecules that sensitize cells to be activated by authentic TLR2 agonists. In both humans and mice, the most relevant natural route of infection with VACV is through intradermal infection of the skin. Therefore, we examined the requirement for …

Anakinra And Related Drugs Targeting Interleukin-1 In The Treatment Of Cryopyrin-Associated Periodic Syndromes, Inessa Bachove, Christopher Chang

Department of Pediatrics Faculty Papers

Anakinra is an interleukin (IL) receptor antagonist that works by blocking the biological activity of IL-1 by competitively inhibiting binding of IL-1 to the type 1 interleukin receptor. IL-1 production is induced in response to inflammatory stimuli and mediates various physiological mechanisms, including inflammation and immunological reactions. Patients with neonatal onset multisystem inflammatory disease (NOMID) produce excess IL-1β, a major proinflammatory cytokine that regulates innate immune responses. Anakinra binds competitively and this results in a rapid reduction in disease severity. NOMID, also known as chronic infantile neurologic, cutaneous, articular syndrome, is the most severe clinical phenotype in the spectrum of …

Induction Of A Type I Interferon Signature In Normal Human Monocytes By Gadolinium-Based Contrast Agents: Comparison Of Linear And Macrocyclic Agents., Peter J. Wermuth, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

The gadolinium-based contrast agent (GdBCA) Omniscan activates human macrophages through Toll-like receptor (TLR)-4 and TLR-7 signalling. To explore the mechanisms responsible we compared the ability of linear and macrocyclic GdBCA to induce a type I interferon signature and a proinflammatory/profibrotic phenotype in normal human monocytes in vitro. Expression of genes associated with type I interferon signalling and inflammation and production of their corresponding proteins were determined. Both linear and macrocyclic GdBCA stimulated expression of multiple type I interferon-regulated genes and the expression of numerous chemokines, cytokines and growth factors in normal human peripheral blood monocytes. There was no correlation between …