Immunopathology Commons^™

Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz

Christian Mueller

Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with ...

A Comparative Analysis Of The West African Hemorrhagic Fevers Caused By The Lassa And Ebola Viruses, Emiene E. Amali-Adekwu

Selected Honors Theses

Lassa fever (LF) and Ebola Hemorrhagic Fever (EHF) are viral diseases endemic to West Africa.The etiological agent of Lassa fever is an enveloped virus from the Arenaviridae family and was first discovered in 1969 when two missionary nurses died of a mysterious illness in the town of Lassa in Borno state, Nigeria.1 This virus is animal-borne (zoonotic) and is carried by the animal vector Mastomys natalensis (multimammate rat). The Ebola virus is also zoonotic originating from fruit bats belonging to the Pteropodidae family.2 The first reported case of Ebola Virus Disease (EVD) was a principal who was ...

The Antiviral Rna Interference Response Provides Resistance To Lethal Arbovirus Infection And Vertical Transmission In Caenorhabditis Elegans, Don B. Gammon, Takao Ishidate, Lichao Li, Weifeng Gu, Neal S. Silverman, Craig C. Mello

University of Massachusetts Medical School Faculty Publications

The recent discovery of the positive-sense single-stranded RNA (ssRNA) Orsay virus (OV) as a natural pathogen of the nematode Caenorhabditis elegans has stimulated interest in exploring virus-nematode interactions. However, OV infection is restricted to a small number of intestinal cells, even in nematodes defective in their antiviral RNA interference (RNAi) response, and is neither lethal nor vertically transmitted. Using a fluorescent reporter strain of the negative-sense ssRNA vesicular stomatitis virus (VSV), we show that microinjection of VSV particles leads to a dose-dependent, muscle tissue-tropic, lethal infection in C. elegans. Furthermore, we find nematodes deficient for components of the antiviral RNAi ...

The Trypanosome Exocyst: A Conserved Structure Revealing A New Role In Endocytosis, Cordula M. Boehm, Samson Obado, Catarina Gadelha, Alexandra Kaupisch, Paul T. Manna, Gwyn W. Gould, Mary Munson, Brian T. Chait, Michael P. Rout, Mark C. Field

Open Access Articles

Membrane transport is an essential component of pathogenesis for most infectious organisms. In African trypanosomes, transport to and from the plasma membrane is closely coupled to immune evasion and antigenic variation. In mammals and fungi an octameric exocyst complex mediates late steps in exocytosis, but comparative genomics suggested that trypanosomes retain only six canonical subunits, implying mechanistic divergence. We directly determined the composition of the Trypanosoma brucei exocyst by affinity isolation and demonstrate that the parasite complex is nonameric, retaining all eight canonical subunits (albeit highly divergent at the sequence level) plus a novel essential subunit, Exo99. Exo99 and Sec15 ...

Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz

UMass Metabolic Network Publications

Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with ...

Characterization Of A Putative Hemolysin Expressed By Sneathia Amnii, A Preterm Birth-Associated Pathogen, Lizette Carrasco, Kimberly Jefferson

Undergraduate Research Posters

The gram-negative bacteria Sneathia amnii is a poorly-characterized commensal of the female urogenital tract frequently associated with adverse clinical outcomes such as bacterial vaginosis (BV), amnionitis, and preterm labor. To investigate its potential role in virulence, we sought to identify and characterize virulence determinants produced by S. amnii in an effort to better understand the pathogenesis of infectious preterm birth. Through sequencing of the Sn35 genome (type strain of S. amnii), we identified two genes with amino acid sequence similarity and structural similarity to the filamentous hemagglutinin (FHA) protein of Bordetella pertussis and its Type Vb transporter. Because S. amnii ...

Biomarkers Of Sepsis: A Retrospective Approach, Jose M. Roberts

Honors Research Projects

Background: Biomarkers are taking the spotlight in becoming the norm for early diagnoses. Sepsis is an inflammatory disease that increases metabolic rate in children. The first biomarker is hyponatremia. Hyponatremia is a frequent electrolyte imbalance in clinical practice, often observed in children with inflammatory disease and infection. Presence of hyponatremia is associated with electrical signaling imbalances, inflammation and renal dysfunction. The clinical value of hyponatremia in pediatric patients is unknown. The C-reactive protein is a second biomarker. Its presence signifies that necrotic cells and inflammation are present.

Objectives: To evaluate the use of biomarkers in children seen in the Emergency ...

Phenotypic Analysis And Localization Of Leukocytes At The Site Of Intradermal Injection Of Phytohemagglutinin In Chickens, Kallie Alyce Sullivan

Theses and Dissertations

Phytohemagglutinin (PHA) is commonly used to gain insight into an individual’s cellular immuno-competence. PHA is typically injected intradermally (i.d.) into the skin (e.g. wing web) and the tissue swelling response is then monitored, whereby the extent of the swelling positively relates to the individual’s cellular immune system capabilities. Although i.d. injected PHA was shown to stimulate mononuclear cell- and basophil-infiltration to the site of injection, reports on temporal, qualitative and quantitative aspects of the local PHA response are limited. The objective of this study was to use the growing feather (GF) as a cutaneous test-site ...

The Rodent Parvovirus H-1 And Its Potential In Combination With Tien Hsien Liquid As A Treatment For Breast Cancer, Hayley I. Spires

Selected Honors Theses

Breast cancer is responsible for 12% of cancer diagnoses each year, and it is the leading cause of cancer-related mortality in women worldwide. Current treatments have provided some success in combatting the disease but are not considered a final solution. The framework for how researchers approach cancer has continued to change, and this includes the introduction of oncolytic viruses as novel therapeutics for cancer. The rodent parvovirus H-1 has shown strong potential in clinical and subclinical trials, but its S phase dependency limits its usefulness against cancer stem cell populations. Tien Hsien Liquid is commerically available, nontoxic, and has shown ...

Distinct Differences On Neointima Formation In Immunodeficient And Humanized Mice After Carotid Or Femoral Arterial Injury, Jill Moser, Joris Van Ark, Marcory C. Van Dijk, Dale L. Greiner, Leonard D. Shultz, Harry Van Goor, Jan-Luuk Hillebrands

Open Access Articles

Percutaneous coronary intervention is widely adopted to treat patients with coronary artery disease. However, restenosis remains an unsolved clinical problem after vascular interventions. The role of the systemic and local immune response in the development of restenosis is not fully understood. Hence, the aim of the current study was to investigate the role of the human immune system on subsequent neointima formation elicited by vascular injury in a humanized mouse model. Immunodeficient NOD.Cg-PrkdcscidIL2rgtm1Wjl(NSG) mice were reconstituted with human (h)PBMCs immediately after both carotid wire and femoral cuff injury were induced in order to identify how differences in ...

A Chimeric Protein-Based Malaria Vaccine Candidate Induces Robust T Cell Responses Against Plasmodium Vivax Msp119, Jairo Andres Fonseca, Monica Cabrera-Mora, Balwan Singh, Joseli Oliveira-Ferreira, Josue Da Costa Lima-Junior, J. Mauricio Calvo-Calle, Jose Manuel Lozano, Alberto Moreno

Open Access Articles

The most widespread Plasmodium species, Plasmodium vivax, poses a significant public health threat. An effective vaccine is needed to reduce global malaria burden. Of the erythrocytic stage vaccine candidates, the 19 kDa fragment of the P. vivax Merozoite Surface Protein 1 (PvMSP119) is one of the most promising. Our group has previously defined several promiscuous T helper epitopes within the PvMSP1 protein, with features that allow them to bind multiple MHC class II alleles. We describe here a P. vivax recombinant modular chimera based on MSP1 (PvRMC-MSP1) that includes defined T cell epitopes genetically fused to PvMSP119. This vaccine candidate ...

Distinct Surveillance Pathway For Immunopathology During Acute Infection Via Autophagy And Sr-Bi, Susanne Pfeiler, Eicke Latz, Bernd Engelmann

Open Access Articles

The mechanisms protecting from immunopathology during acute bacterial infections are incompletely known. We found that in response to apoptotic immune cells and live or dead Listeria monocytogenes scavenger receptor BI (SR-BI), an anti-atherogenic lipid exchange mediator, activated internalization mechanisms with characteristics of macropinocytosis and, assisted by Golgi fragmentation, initiated autophagic responses. This was supported by scavenger receptor-induced local increases in membrane cholesterol concentrations which generated lipid domains particularly in cell extensions and the Golgi. SR-BI was a key driver of beclin-1-dependent autophagy during acute bacterial infection of the liver and spleen. Autophagy regulated tissue infiltration of neutrophils, suppressed accumulation of ...

Surveillance Immunity: An Emerging Paradigm Of Innate Defense Activation In Caenorhabditis Elegans, Read Pukkila-Worley

Open Access Articles

No abstract provided.

Pd-L1 Expression In Ebv-Negative Diffuse Large B-Cell Lymphoma: Clinicopathologic Features And Prognostic Implications, Wei Xing, Karen A. Dresser, Rui Zhang, Andrew M. Evens, Hongbo Yu, Bruce A. Woda, Benjamin J. Chen

Open Access Articles

Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were ...

A Fluorescent Reporter Mouse For Inflammasome Assembly Demonstrates An Important Role For Cell-Bound And Free Asc Specks During In Vivo Infection, Te-Chen Tzeng, Stefan A. Schattgen, Brian G. Monks, Donghai Wang, Anna M. Cerny, Eicke Latz, Katherine A. Fitzgerald, Douglas T. Golenbock

Open Access Articles

Inflammasome activation is associated with numerous diseases. However, in vivo detection of the activated inflammasome complex has been limited by a dearth of tools. We have developed transgenic mice that ectopically express the fluorescent adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and characterized the formation of assembled inflammasome complexes ("specks") in primary cells and tissues. In addition to hematopoietic cells, we have found that a stromal population in the lung tissues formed specks during the early phase of influenza infection, whereas myeloid cells showed speck formation after 2 days. In a peritonitis and group B streptococcus ...

Channa Striatus Tnfr-1: Molecular Cloning, Characterization And Gene Expression, Rajesh Palanisamy

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.

Border Security: The Role Of Ripk3 In Epithelium Homeostasis, Kenta Moriwaki, Sakthi Balaji, Francis Ka-Ming Chan

Open Access Articles

Receptor interacting protein kinase 3 (RIPK3) is a crucial inducer of necroptosis. Its activity is controlled by interaction with other signal adaptors through the "RIP homotypic interaction motif" (RHIM). Recent studies revealed a critical function for RIPK3 in the maintenance of epithelial tissue integrity. In mice with genetic deficiency of the apoptosis adaptors FADD or caspase 8, RIPK3 promotes necroptotic cell death of epithelial cells, leading to excessive and lethal inflammation. In contrast, when FADD and caspase 8 functions are intact, RIPK3 serves as a protector of intestinal epithelial integrity by promoting injury-induced wound repair. In the latter case, RIPK3 ...

Gene Expression Of Interleukin 8 In Liver Of Japanese Flounder Paralichthys Olivaceus Infected With Edwardsiella Tarda, Osamu Kurata, Shinpei Wada

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.

Il-2 And Il-6 Cooperate To Enhance The Generation Of Influenza-Specific Cd8 T Cells Responding To Live Influenza Virus In Aged Mice And Humans, Xin Zhou, Jacob W. Hopkins, Chongkai Wang, Vinayak Brahmakshatriya, Susan L. Swain, George A. Kuchel, Laura Haynes, Janet E. Mcelhaney

Open Access Articles

An age-related decline in cytolytic activity has been described in CD8+ T cells and we have previously shown that the poor CD8+ effector T cell responses to influenza A/H3N2 challenge result from a decline in the proportion and function of these cytolytic T lymphocytes (CTL). Here, we describe that addition of exogenous cytokines to influenza-stimulated PBMC from both aged mice and humans, enhances the generation of influenza specific CD8 CTL by increasing their proliferation and survival. Our data show that the addition of IL-2 and IL-6 to splenocytes from mice previously infected with influenza virus restores the aged CD8 ...

Reassessing The Role Of The Nlrp3 Inflammasome During Pathogenic Influenza A Virus Infection Via Temporal Inhibition, Michelle D. Tate, James D.H. Ong, Jennifer K. Dowling, Julie L. Mcauley, Avril B. Robertson, Eicke Latz, Grant R. Drummond, Matthew A. Cooper, Paul J. Hertzog, Ashley Mansell

Open Access Articles

The inflammasome NLRP3 is activated by pathogen associated molecular patterns (PAMPs) during infection, including RNA and proteins from influenza A virus (IAV). However, chronic activation by danger associated molecular patterns (DAMPs) can be deleterious to the host. We show that blocking NLRP3 activation can be either protective or detrimental at different stages of lethal influenza A virus (IAV). Administration of the specific NLRP3 inhibitor MCC950 to mice from one day following IAV challenge resulted in hypersusceptibility to lethality. In contrast, delaying treatment with MCC950 until the height of disease (a more likely clinical scenario) significantly protected mice from severe and ...