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Acute Symptomatic Influenza A Virus (Iav) Infection In Humans Leads To Expansion Of Highly Diverse Cd8 T Cell Repertoires Crossreactive With Persistent Epstein Barr Virus (Ebv), Anna Gil, Rabinarayan Misha, Nuray Aslan, Liisa K. Selin 2014 University of Massachusetts Medical School

Acute Symptomatic Influenza A Virus (Iav) Infection In Humans Leads To Expansion Of Highly Diverse Cd8 T Cell Repertoires Crossreactive With Persistent Epstein Barr Virus (Ebv), Anna Gil, Rabinarayan Misha, Nuray Aslan, Liisa K. Selin

UMass Center for Clinical and Translational Science Research Retreat

The competence of T cell responses predominantly depends on how efficient T cell receptors (TCRs) are at recognizing antigenic epitopes. We show here that during acute severely symptomatic IAV infection there was an expansion of IAV-M1/EBV-BRLF1 and IAV-M1/EBV-BMLF1 double-tetramer+ cells directly ex-vivo in 5 HLA-A2+ patients. We questioned whether this expansion specific to these two different crossreactive responses would lead to alterations in the TCR repertoire of the IAV-M158 , EBV-BRLF1109 and -BMLF1280 from before, during and following acute IAV infection. Using staining with Vb MAb we found that T cell responses generated to these epitopes became surprisingly more ...


Severity Of Infectious Mononucleosis (Im) Correlates With The Frequency Of Crossreactive Influenza A Virus (Iav)-M1 And Epstein Barr Virus (Ebv)-Bmlf-1-Specific Cd8 T Cells, Nuray Aslan, Levi B. Watkin, Anna Gil, Katherine Luzuriaga, Liisa K. Selin 2014 University of Massachusetts Medical School

Severity Of Infectious Mononucleosis (Im) Correlates With The Frequency Of Crossreactive Influenza A Virus (Iav)-M1 And Epstein Barr Virus (Ebv)-Bmlf-1-Specific Cd8 T Cells, Nuray Aslan, Levi B. Watkin, Anna Gil, Katherine Luzuriaga, Liisa K. Selin

UMass Center for Clinical and Translational Science Research Retreat

During EBV-associated IM IAV-specific crossreactive memory T cells are activated and play a role in disease severity. In HLA-A2+ IM patients, influenza M158 (IAV-M1)-specific CD8 memory T cell responses crossreacted with two different EBV lytic epitopes, BMLF1280 (17/29) and BRLF1190 (19/20). Furthermore, 11/22 IM patients demonstrated some intra-viral crossreactivity between EBV-BRLF1 and -BMLF1 responses. Disease severity of IM directly correlated with significantly increased frequencies of crossreactive IAV-M1/EBV-BMLF1, IAV-M1, and EBV-BMLF1 specific CD8 cells, and with mean viral load over the first 5 weeks of infection. Disease severity did not correlate with BRLF1 or M1/BRLF1 ...


Epstein-Barr Virus (Ebv)-Lytic Cross-Reactive Influenza-A (Iav) Memory Cd8 T-Cells In Ebv Sero-Negative Middle-Aged Adults, Rabinarayan Mishra, Levi B. Watkin, Nuray Aslan, Anna Gil, Katherine Ruiz De Luzuriaga, Liisa K. Selin 2014 University of Massachusetts Medical School

Epstein-Barr Virus (Ebv)-Lytic Cross-Reactive Influenza-A (Iav) Memory Cd8 T-Cells In Ebv Sero-Negative Middle-Aged Adults, Rabinarayan Mishra, Levi B. Watkin, Nuray Aslan, Anna Gil, Katherine Ruiz De Luzuriaga, Liisa K. Selin

UMass Center for Clinical and Translational Science Research Retreat

EBV is a common human pathogen, which infects ~90% of people and establishes a life-long chronic infection. The clinical outcomes of acute infection can range from asymptomatic to severe immunopathology such as infectious mononucleosis (IM). However, for unknown reasons 5-10% of middle-aged adults (>35 years) remain EBV-seronegative (EBV-SN) when the virus infects the vast majority of people, and is actively shed at high titers during chronic infection. Here we show that EBV-SN (ASN) HLA-A2+ middle-aged adults possess a unique IAV-M1-GIL58-66 memory CD8 T-cell response that cross-reacts with EBV lytic epitopes that differs from teenage EBV-SN (TSN) (18-19 years) and EBV-seropositive ...


Crossreactive Epstein-Barr Virus (Ebv)-Influenza A Virus (Iav) Specific Cd8 Memory T Cells During Acute Symptomatic Iav Infection, Rabinarayan Mishra, Anna Gil, Nuray Aslan, Katherine Ruiz De Luzuriaga, Liisa K. Selin 2014 University of Massachusetts Medical School

Crossreactive Epstein-Barr Virus (Ebv)-Influenza A Virus (Iav) Specific Cd8 Memory T Cells During Acute Symptomatic Iav Infection, Rabinarayan Mishra, Anna Gil, Nuray Aslan, Katherine Ruiz De Luzuriaga, Liisa K. Selin

UMass Center for Clinical and Translational Science Research Retreat

We previously showed that crossreactivity is common between IAV and EBV in HLA-A2+ patients during infectious mononucleosis. IAV-M1-GIL58-66 specific CD8 T cells, along with expanded populations of IAV-M1-GIL58-66/EBV-BRLF-1109-117 -YVL and IAV-M1-GIL58-66/EBV-BMLF1280-288-GLC double-tetramer+ cells were detected directly ex-vivo in 5 HLA-A2+ patients. Altered IAV-M158-66, EBV-BRLF1119-117 and -BMLF1280-288 TCR repertoires were observed over the course of infection and in comparison to healthy donors. After culture, cells were sorted and analyzed by gene array in order to assess global changes in immune responses following different stimulations, either cognate or crossreactive, in different patient populations. M1-GIL and BRLF1-YVL specific cells had similar ...


Caspase-8 And Rip Kinases Regulate Bacteria-Induced Innate Immune Responses And Cell Death, Dan Weng, Robyn Lynn Marty-Roix, Sandhya Ganesan, Megan K. Proulx, Gregory I. Vladimer, William J. Kaiser, Edward S. Mocarski, Kimberly Lea Pouliot, Francis Ka-Ming Chan, Michelle A. Kelliher, Phillip A. Harris, John Bertin, Peter J. Gough, Dmitry M. Shayakhmetov, Jon D. Goguen, Katherine A. Fitzgerald, Neal S. Silverman, Egil Lien 2014 University of Massachusetts Medical School

Caspase-8 And Rip Kinases Regulate Bacteria-Induced Innate Immune Responses And Cell Death, Dan Weng, Robyn Lynn Marty-Roix, Sandhya Ganesan, Megan K. Proulx, Gregory I. Vladimer, William J. Kaiser, Edward S. Mocarski, Kimberly Lea Pouliot, Francis Ka-Ming Chan, Michelle A. Kelliher, Phillip A. Harris, John Bertin, Peter J. Gough, Dmitry M. Shayakhmetov, Jon D. Goguen, Katherine A. Fitzgerald, Neal S. Silverman, Egil Lien

GSBS Student Publications

A number of pathogens cause host cell death upon infection, and Yersinia pestis, infamous for its role in large pandemics such as the "Black Death" in medieval Europe, induces considerable cytotoxicity. The rapid killing of macrophages induced by Y. pestis, dependent upon type III secretion system effector Yersinia outer protein J (YopJ), is minimally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF. Caspase-8 is known to mediate apoptotic death in response to infection with several viruses and to regulate programmed necrosis (necroptosis), but its role in bacterially induced cell death is poorly understood. Here we provide genetic ...


Phthalates And Phthalate Alternatives: Effects On Proliferative And Estrogenic Target Genes In Ishikawa Cells, Ranjani Sundar '15, Ping Yin, Serdar E. Bulun 2014 Illinois Mathematics and Science Academy

Phthalates And Phthalate Alternatives: Effects On Proliferative And Estrogenic Target Genes In Ishikawa Cells, Ranjani Sundar '15, Ping Yin, Serdar E. Bulun

Student Publications & Research

Phthalates are used as plasticizers in many of the products found in medical, household, and industrial applications. Much research has not been completed on the effects of these phthalates as potential endocrine disrupting chemicals (EDCs). As these chemicals are ingested, the mechanism by which they affect the reproductive system is largely unknown. The purpose of this study was to observe how 2 phthalates, Di-n-butyl phthalate (DBP) and Diisononyl phthalate (DINP), and 2 phthalate alternatives, Dioctyl terephthalate (DOTP) and BHT (butylated hydroxytoluene)affect uterine cells in comparison to a vehicle treatment and 17β-Estradiol treatment. Changes in expression of mRNA were observed ...


Alteration Of Intestinal Microbiota In Response To Induced Immune System, Hao Tran, Andrew T. Gewirtz, Benoit Chassaing 2014 Georgia State University

Alteration Of Intestinal Microbiota In Response To Induced Immune System, Hao Tran, Andrew T. Gewirtz, Benoit Chassaing

Georgia State Undergraduate Research Conference

No abstract provided.


Regulation Of Type Ii Responses In Lung Fibrosis And Systemic Autoimmunity: A Dissertation, Tia Bumpus Brodeur 2014 University of Massachusetts Medical School Worcester

Regulation Of Type Ii Responses In Lung Fibrosis And Systemic Autoimmunity: A Dissertation, Tia Bumpus Brodeur

GSBS Dissertations and Theses

Preclinical models of lupus indicate that T cell-B cell collaboration drives antinuclear antibody (ANA) production and sustains T cell activation. Autoreactive B lymphocytes are present in the normal repertoire but persist as ignorant or anergic cells. Mechanisms that normally limit T cell activation of autoreactive B cells remain incompletely resolved, but potentially include the absence of autoreactive effector T cell subsets and/or the presence of autoAgspecific regulatory T cells (Tregs). Several studies have addressed this issue by using experimental systems dependent on transgenic autoreactive B cells, but much less is known about the activation of autoreactive B cells present ...


Cd8+ T Cell And Nk Responses To A Novel Dengue Epitope: A Possible Role For Kir3dl1 In Dengue Pathogenesis: A Dissertation, Elizabeth Townsley 2014 University of Massachusetts Medical School

Cd8+ T Cell And Nk Responses To A Novel Dengue Epitope: A Possible Role For Kir3dl1 In Dengue Pathogenesis: A Dissertation, Elizabeth Townsley

GSBS Dissertations and Theses

Variation in the sequence of T cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T cell responses during second heterologous infections contributing to pathology following DENV infection. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein, NS126-34. We predicted higher frequencies of NS126-34-specific CD8+ T cells in PBMC from individuals undergoing secondary, rather than primary, DENV infection due to the expansion of memory CD8+T cells. We generated a tetramer against this epitope (B57-NS126-34TET) and used it to assess the frequencies and phenotype of antigen-specific T cells ...


My_Story_With_Celiac, 2014 Kuwait University

My_Story_With_Celiac

arditahaskoceloj@yahoo.com

#CELIAC #AWARENESS #TEAM #KUWAIT


Outer Membrane Protein P5 Is Required For Resistance Of Nontypeable Haemophilus Influenzae To Both The Classical And Alternative Complement Pathways, Charles V. Rosadini, Sanjay Ram, Brian J. Akerley 2014 University of Massachussetts Medical School

Outer Membrane Protein P5 Is Required For Resistance Of Nontypeable Haemophilus Influenzae To Both The Classical And Alternative Complement Pathways, Charles V. Rosadini, Sanjay Ram, Brian J. Akerley

University of Massachusetts Medical School Faculty Publications

The complement system is an important first line of defense against the human pathogen Haemophilus influenzae. To survive and propagate in vivo, H. influenzae has evolved mechanisms for subverting this host defense, most of which have been shown to involve outer surface structures, including lipooligosaccharide glycans and outer surface proteins. Bacterial defense against complement acts at multiple steps in the pathway by mechanisms that are not fully understood. Here we identify outer membrane protein P5 as an essential factor in serum resistance of both H. influenzae strain Rd and nontypeable H. influenzae (NTHi) clinical isolate NT127. P5 was essential for ...


Therapeutic Depletion Of Natural Killer Cells Controls Persistent Infection, Stephen N. Waggoner, Keith A. Daniels, Raymond M. Welsh 2014 University of Massachusetts Medical School

Therapeutic Depletion Of Natural Killer Cells Controls Persistent Infection, Stephen N. Waggoner, Keith A. Daniels, Raymond M. Welsh

University of Massachusetts Medical School Faculty Publications

Persistent viral infections are associated with host and viral factors that impair effective antiviral immunity. Natural killer (NK) cells contribute to establishment of persistent lymphocytic choriomeningitis virus (LCMV) infection in mice through suppression of virus-specific T cell responses during the first few days of infection, but NK cell depletion during those early time points can enable severe T cell-mediated immune pathology and death of the host. Here we show that long after their peak in cytolytic activation, NK cells continue to support viral persistence at later times of infection. Delayed depletion of NK cells, 2 to 3 weeks after infection ...


Blockade Of Mast Cell Activation Reduces Cutaneous Scar Formation, Lin Chen, Megan Schrementi, Matthew J. Ranzer, Traci A. Wilgus, Luisa A. DiPietro 2014 Illinois Mathematics and Science Academy

Blockade Of Mast Cell Activation Reduces Cutaneous Scar Formation, Lin Chen, Megan Schrementi, Matthew J. Ranzer, Traci A. Wilgus, Luisa A. Dipietro

Faculty Publications & Research

Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair ...


Inkt Cell Production Of Gm-Csf Controls Mycobacterium Tuberculosis, Alissa C. Rothchild, Pushpa Jayaraman, Claudio Nunes-Alves, Samuel M. Behar 2014 University of Massachusetts Medical School Worcester

Inkt Cell Production Of Gm-Csf Controls Mycobacterium Tuberculosis, Alissa C. Rothchild, Pushpa Jayaraman, Claudio Nunes-Alves, Samuel M. Behar

University of Massachusetts Medical School Faculty Publications

Invariant natural killer T (iNKT) cells are activated during infection, but how they limit microbial growth is unknown in most cases. We investigated how iNKT cells suppress intracellular Mycobacterium tuberculosis (Mtb) replication. When co-cultured with infected macrophages, iNKT cell activation, as measured by CD25 upregulation and IFNgamma production, was primarily driven by IL-12 and IL-18. In contrast, iNKT cell control of Mtb growth was CD1d-dependent, and did not require IL-12, IL-18, or IFNgamma. This demonstrated that conventional activation markers did not correlate with iNKT cell effector function during Mtb infection. iNKT cell control of Mtb replication was also independent of ...


Role Of Viral And Host Factors In Influenza Virus Mediated Inhibition Of Interleukin-23, Ashish Tiwari 2014 University of Kentucky

Role Of Viral And Host Factors In Influenza Virus Mediated Inhibition Of Interleukin-23, Ashish Tiwari

Theses and Dissertations--Veterinary Science

Influenza virus is one of the major respiratory pathogens of humans as well as animals, including equines. There is an increasing evidence that bacterial infections are the most common cause of the death during influenza. In horses also, secondary bacterial pneumonia can lead to death, and surviving horses may take up to six months for the complete recovery resulting in heavy economic loss to the equine industry. Interleukin (IL)-23 mediated innate immune response has been shown to protect the host from various respiratory bacterial infections. However, studies to investigate the role of host and viral factors in the regulation ...


Amphotericin B Increases Influenza A Virus Infection By Preventing Ifitm3-Mediated Restriction, Tsai-Yu Lin, Christopher R. Chin, Aaron R. Everitt, Simon Clare, Jill Perreira, George Savidis, Aaron M. Aker, Sinu P. John, David Sarlah, Erick M. Carreira, Stephen J. Elledge, Paul Kellam, Abraham L. Brass 2013 University of Massachusetts Medical School

Amphotericin B Increases Influenza A Virus Infection By Preventing Ifitm3-Mediated Restriction, Tsai-Yu Lin, Christopher R. Chin, Aaron R. Everitt, Simon Clare, Jill Perreira, George Savidis, Aaron M. Aker, Sinu P. John, David Sarlah, Erick M. Carreira, Stephen J. Elledge, Paul Kellam, Abraham L. Brass

University of Massachusetts Medical School Faculty Publications

The IFITMs inhibit influenza A virus (IAV) replication in vitro and in vivo. Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication. Consistent with its neutralization of IFITM3, a clinical preparation of AmphoB, AmBisome, reduces the majority of interferon's protective effect against IAV in vitro. Mechanistic studies reveal that IFITM1 decreases host-membrane fluidity, suggesting both a possible mechanism for IFITM-mediated restriction and its negation by AmphoB. Notably, we reveal that mice treated with AmBisome succumbed to a normally mild IAV infection, similar to animals deficient in Ifitm3. Therefore, patients ...


Long-Lasting T Cell-Independent Igg Responses Require Myd88-Mediated Pathways And Are Maintained By High Levels Of Virus Persistence, Forum M. Raval, Rabinarayan Mishra, Robert L. Garcea, Raymond M. Welsh, Eva Szomolanyi-Tsuda 2013 University of Massachusetts Medical School

Long-Lasting T Cell-Independent Igg Responses Require Myd88-Mediated Pathways And Are Maintained By High Levels Of Virus Persistence, Forum M. Raval, Rabinarayan Mishra, Robert L. Garcea, Raymond M. Welsh, Eva Szomolanyi-Tsuda

Pathology Publications and Presentations

Many viruses induce acute T cell-independent (TI) B cell responses due to their repetitive epitopes and the induction of innate cytokines. Nevertheless, T cell help is thought necessary for the development of long-lasting antiviral antibody responses in the form of long-lived plasma cells and memory B cells. We found that T cell-deficient (T cell receptor beta and delta chain [TCRbetadelta] knockout [KO]) mice persistently infected with polyomavirus (PyV) had long-lasting antiviral serum IgG, and we questioned whether they could generate TI B cell memory. TCRbetadelta KO mice did not form germinal centers after PyV infection, lacked long-lived IgG-secreting plasma cells ...


Rage Is A Nucleic Acid Receptor That Promotes Inflammatory Responses To Dna, Cherilyn M. Sirois, Tengchuan Jin, Allison L. Miller, Damien Bertheloot, Hirotaka Nakamura, Gabor Horvath, Abubakar Mian, Jiansheng Jiang, Jacob Schrum, Lukas Bossaller, Karin Pelka, Natalio Garbi, Yambasu Brewah, Jane Tian, ChewShun Chang, Partha S. Chowdhury, Gary P. Sims, Roland Kolbeck, Anthony J. Coyle, Alison A. Humbles, T. Sam Xiao, Eicke Latz 2013 University of Massachusetts Medical School

Rage Is A Nucleic Acid Receptor That Promotes Inflammatory Responses To Dna, Cherilyn M. Sirois, Tengchuan Jin, Allison L. Miller, Damien Bertheloot, Hirotaka Nakamura, Gabor Horvath, Abubakar Mian, Jiansheng Jiang, Jacob Schrum, Lukas Bossaller, Karin Pelka, Natalio Garbi, Yambasu Brewah, Jane Tian, Chewshun Chang, Partha S. Chowdhury, Gary P. Sims, Roland Kolbeck, Anthony J. Coyle, Alison A. Humbles, T. Sam Xiao, Eicke Latz

University of Massachusetts Medical School Faculty Publications

Recognition of DNA and RNA molecules derived from pathogens or self-antigen is one way the mammalian immune system senses infection and tissue damage. Activation of immune signaling receptors by nucleic acids is controlled by limiting the access of DNA and RNA to intracellular receptors, but the mechanisms by which endosome-resident receptors encounter nucleic acids from the extracellular space are largely undefined. In this study, we show that the receptor for advanced glycation end-products (RAGE) promoted DNA uptake into endosomes and lowered the immune recognition threshold for the activation of Toll-like receptor 9, the principal DNA-recognizing transmembrane signaling receptor. Structural analysis ...


Salicylate Prevents Virus-Induced Type 1 Diabetes In The Bbdr Rat, Chaoxing Yang, Agata Jurczyk, Philip J. diIorio, Elaine Norowski, Michael A. Brehm, Christian W. Grant, Dennis L. Guberski, Dale L. Greiner, Rita Bortell 2013 University of Massachusetts Medical School

Salicylate Prevents Virus-Induced Type 1 Diabetes In The Bbdr Rat, Chaoxing Yang, Agata Jurczyk, Philip J. Diiorio, Elaine Norowski, Michael A. Brehm, Christian W. Grant, Dennis L. Guberski, Dale L. Greiner, Rita Bortell

Open Access Articles

Epidemiologic and clinical evidence suggests that virus infection plays an important role in human type 1 diabetes pathogenesis. We used the virus-inducible BioBreeding Diabetes Resistant (BBDR) rat to investigate the ability of sodium salicylate, a non-steroidal anti-inflammatory drug (NSAID), to modulate development of type 1 diabetes. BBDR rats treated with Kilham rat virus (KRV) and polyinosinic:polycytidylic acid (pIC, a TLR3 agonist) develop diabetes at nearly 100% incidence by ~2 weeks. We found distinct temporal profiles of the proinflammatory serum cytokines, IL-1beta, IL-6, IFN-gamma, IL-12, and haptoglobin (an acute phase protein) in KRV+pIC treated rats. Significant elevations of IL-1beta ...


Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo 2013 University of Massachusetts Medical School

Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo

Gastroenterology Publications and Presentations

Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis ...


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