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Humoral And Cell-Mediated Immune Response In Colostrum From Women Diagnosed Positive For Sars-Cov-2, Vignesh Narayanaswamy, Brian Pentecost, Dominique Alfandari, Emily Chin, Kathleen Minor, Alyssa Kastrinakis, Tanya Lieberman, Kathleen F. Arcaro, Heidi Leftwich 2021 University of Massachusetts Amherst

Humoral And Cell-Mediated Immune Response In Colostrum From Women Diagnosed Positive For Sars-Cov-2, Vignesh Narayanaswamy, Brian Pentecost, Dominique Alfandari, Emily Chin, Kathleen Minor, Alyssa Kastrinakis, Tanya Lieberman, Kathleen F. Arcaro, Heidi Leftwich

COVID-19 Publications by UMass Chan Authors

Objective: To evaluate the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in colostrum from women who tested positive for the virus.

Methods: Between March and September 2020 we obtained bilateral colostrum samples collected on spot cards within 48 hours of delivery from 15 new mothers who had previously tested positive for SARS-CoV-2. Four of 15 women provided liquid colostrum, which was used for validating results obtained from spot cards. Archived bilateral colostrum samples collected from 8 women during 2011-2013 were used as pre-coronavirus disease 2019 (COVID-19) controls. All samples were tested for reactivity to the receptor binding ...


May-Thurner Compressive Syndrome Unmasked By Rapid Weight Loss, Hesham A. Hassan, Jan-Paul Sambataro, James C. Abraham 2021 Brandon Regional Hospital

May-Thurner Compressive Syndrome Unmasked By Rapid Weight Loss, Hesham A. Hassan, Jan-Paul Sambataro, James C. Abraham

HCA Healthcare Journal of Medicine

May-Thurner Syndrome (MTS) is an anatomical syndrome characterized by a predisposition to clot formation when there is compression of the left iliac vein by the right iliac artery. In this case, we discuss an atypical presentation of MTS in a young male after rapid weight loss. The patient was admitted for an unprovoked massive proximal deep vein thrombosis (DVT) after a two-hundred-pound weight loss during the preceding six-month period. Treatment involved mechanical thrombectomy by interventional radiology, initiation of apixaban and recommended follow up with vascular surgery for angioplasty instead of immediate stent placement.


A Diamidobenzimidazole Sting Agonist Protects Against Sars-Cov-2 Infection, Fiachra Humphries, Liraz Shmuel-Galia, Zhaozhao Jiang, Ruth Wilson, Philip Landis, Sze-Ling Ng, Krishna M. Parsi, Rene Maehr, John Cruz, Angel Morales-Ramos, Joshi M. Ramanjulu, John Bertin, G. Scott Pesiridis, Katherine A. Fitzgerald 2021 University of Massachusetts Medical School

A Diamidobenzimidazole Sting Agonist Protects Against Sars-Cov-2 Infection, Fiachra Humphries, Liraz Shmuel-Galia, Zhaozhao Jiang, Ruth Wilson, Philip Landis, Sze-Ling Ng, Krishna M. Parsi, Rene Maehr, John Cruz, Angel Morales-Ramos, Joshi M. Ramanjulu, John Bertin, G. Scott Pesiridis, Katherine A. Fitzgerald

COVID-19 Publications by UMass Chan Authors

Coronaviruses are a family of RNA viruses that cause acute and chronic diseases of the upper and lower respiratory tract in humans and other animals. SARS-CoV-2 is a recently emerged coronavirus that has led to a global pandemic causing a severe respiratory disease known as COVID-19 with significant morbidity and mortality worldwide. The development of antiviral therapeutics are urgently needed while vaccine programs roll out worldwide. Here we describe a diamidobenzimidazole compound, diABZI-4, that activates STING and is highly effective in limiting SARS-CoV-2 replication in cells and animals. diABZI-4 inhibited SARS-CoV-2 replication in lung epithelial cells. Administration of diABZI-4 intranasally ...


Tissue-Resident-Like Cd4+ T Cells Secreting Il-17 Control Mycobacterium Tuberculosis In The Human Lung, Paul Ogongo, Liku B. Tezera, Amanda Ardain, Shepherd Nhamoyebonde, Duran Ramsuran, Alveera Singh, Abigail Ng'oepe, Farina Karim, Taryn Naidoo, Khadija Khan, Kaylesh J. Dullabh, Michael Fehlings, Boon Heng. Lee, Alessandra Nardin, Cecilia S. Lindestam Arlehamn, Alessandro Sette, Samuel M. Behar, Adrie Jc. Steyn, Rajhmun Madansein, Henrik N. Kloverpris, Paul T. Elkington, Alasdair Leslie 2021 University of KwaZulu-Natal

Tissue-Resident-Like Cd4+ T Cells Secreting Il-17 Control Mycobacterium Tuberculosis In The Human Lung, Paul Ogongo, Liku B. Tezera, Amanda Ardain, Shepherd Nhamoyebonde, Duran Ramsuran, Alveera Singh, Abigail Ng'oepe, Farina Karim, Taryn Naidoo, Khadija Khan, Kaylesh J. Dullabh, Michael Fehlings, Boon Heng. Lee, Alessandra Nardin, Cecilia S. Lindestam Arlehamn, Alessandro Sette, Samuel M. Behar, Adrie Jc. Steyn, Rajhmun Madansein, Henrik N. Kloverpris, Paul T. Elkington, Alasdair Leslie

Open Access Publications by UMass Chan Authors

T cell immunity is essential for the control of tuberculosis (TB), an important disease of the lung, and is generally studied in humans using peripheral blood cells. Mounting evidence, however, indicates that tissue-resident memory T cells (Trms) are superior at controlling many pathogens, including Mycobacterium tuberculosis (M. tuberculosis), and can be quite different from those in circulation. Using freshly resected lung tissue, from individuals with active or previous TB, we identified distinct CD4+ and CD8+ Trm-like clusters within TB-diseased lung tissue that were functional and enriched for IL-17-producing cells. M. tuberculosis-specific CD4+ T cells producing TNF-alpha, IL-2, and IL-17 were ...


Bleeding Disorder Referrals To Hematology Clinic: A Single Institution Experience, Zuri Hudson 2021 Children's Mercy Kansas City

Bleeding Disorder Referrals To Hematology Clinic: A Single Institution Experience, Zuri Hudson

Research Days

Background: Our center receives hundreds of referrals yearly for bleeding disorder evaluation both due to bleeding symptoms and secondary to routine preoperative laboratory testing. The evaluation for a bleeding disorder can be challenging due to the wide variability of symptoms as well as the need for accurately interpreting lab results. Bhasin et al showed that 4% of patients referred to hematology based on a preoperative coagulation evaluation had a clinically relevant bleeding disorder. Currently there is little published about the referral patterns to pediatric hematology and the outcomes of these referrals.

Objectives/Goal: To characterize our hematology referrals for bleeding ...


Distinguishing Signal From Noise In Immunopeptidome Studies Of Limiting-Abundance Biological Samples: Peptides Presented By I-A(B) In C57bl/6 Mouse Thymus, Padma P. Nanaware, Mollie M. Jurewicz, Cristina C. Clement, Liying Lu, Laura Santambrogio, Lawrence J. Stern 2021 University of Massachusetts Medical School

Distinguishing Signal From Noise In Immunopeptidome Studies Of Limiting-Abundance Biological Samples: Peptides Presented By I-A(B) In C57bl/6 Mouse Thymus, Padma P. Nanaware, Mollie M. Jurewicz, Cristina C. Clement, Liying Lu, Laura Santambrogio, Lawrence J. Stern

Open Access Publications by UMass Chan Authors

Antigen presentation by MHC-II proteins in the thymus is central to selection of CD4 T cells, but analysis of the full repertoire of presented peptides responsible for positive and negative selection is complicated by the low abundance of antigen presenting cells. A key challenge in analysis of limiting abundance immunopeptidomes by mass spectrometry is distinguishing true MHC-binding peptides from co-eluting non-specifically bound peptides present in the mixture eluted from immunoaffinity-purified MHC molecules. Herein we tested several approaches to minimize the impact of non-specific background peptides, including analyzing eluates from isotype-control antibody-conjugated beads, considering only peptides present in nested sets, and ...


Novel Combinatorial Microrna-Binding Sites In Aav Vectors Synergistically Diminish Antigen Presentation And Transgene Immunity For Efficient And Stable Transduction, Manish Muhuri, Wei Zhan, Yukiko Maeda Garrison, Jia Li, Anoushka Lotun, Jennifer Chen, Katelyn E. Sylvia, Ishani Dasgupta, Motahareh Arjomandnejad, Thomas Nixon, Allison M. Keeler, Sangeetha Manokaran, Ran He, Qin Su, Phillip W. L. Tai, Guangping Gao 2021 University of Massachusetts Medical School

Novel Combinatorial Microrna-Binding Sites In Aav Vectors Synergistically Diminish Antigen Presentation And Transgene Immunity For Efficient And Stable Transduction, Manish Muhuri, Wei Zhan, Yukiko Maeda Garrison, Jia Li, Anoushka Lotun, Jennifer Chen, Katelyn E. Sylvia, Ishani Dasgupta, Motahareh Arjomandnejad, Thomas Nixon, Allison M. Keeler, Sangeetha Manokaran, Ran He, Qin Su, Phillip W. L. Tai, Guangping Gao

Open Access Publications by UMass Chan Authors

Recombinant adeno-associated virus (rAAV) platforms hold promise for in vivo gene therapy but are undermined by the undesirable transduction of antigen presenting cells (APCs), which in turn can trigger host immunity towards rAAV-expressed transgene products. In light of recent adverse events in patients receiving high systemic AAV vector doses that were speculated to be related to host immune responses, development of strategies to mute innate and adaptive immunity is imperative. The use of miRNA binding sites (miR-BSs) to confer endogenous miRNA-mediated regulation to detarget transgene expression from APCs has shown promise for reducing transgene immunity. Studies have shown that designing ...


Mesenchymal Stromal Cell-Derived Extracellular Vesicles Restore Thymic Architecture And T Cell Function Disrupted By Neonatal Hyperoxia, Monica Reis, Gareth R. Willis, Angeles Fernandez-Gonzalez, Vincent Yeung, Elizabeth Taglauer, Margaret Magaletta, Teagan J. Parsons, Alan G. Derr, Xianlan Liu, Rene Maehr, Stella Kourembanas, S. Alex Mitsialis 2021 Harvard Medical School

Mesenchymal Stromal Cell-Derived Extracellular Vesicles Restore Thymic Architecture And T Cell Function Disrupted By Neonatal Hyperoxia, Monica Reis, Gareth R. Willis, Angeles Fernandez-Gonzalez, Vincent Yeung, Elizabeth Taglauer, Margaret Magaletta, Teagan J. Parsons, Alan G. Derr, Xianlan Liu, Rene Maehr, Stella Kourembanas, S. Alex Mitsialis

Open Access Publications by UMass Chan Authors

Treating premature infants with high oxygen is a routine intervention in the context of neonatal intensive care. Unfortunately, the increase in survival rates is associated with various detrimental sequalae of hyperoxia exposure, most notably bronchopulmonary dysplasia (BPD), a disease of disrupted lung development. The effects of high oxygen exposure on other developing organs of the infant, as well as the possible impact such disrupted development may have on later life remain poorly understood. Using a neonatal mouse model to investigate the effects of hyperoxia on the immature immune system we observed a dramatic involution of the thymic medulla, and this ...


Cancer Immune Evasion Through Loss Of Mhc Class I Antigen Presentation, Karthik Dhatchinamoorthy, Jeff D. Colbert, Kenneth L. Rock 2021 University of Massachusetts Medical School

Cancer Immune Evasion Through Loss Of Mhc Class I Antigen Presentation, Karthik Dhatchinamoorthy, Jeff D. Colbert, Kenneth L. Rock

Open Access Publications by UMass Chan Authors

Major histocompatibility class I (MHC I) molecules bind peptides derived from a cell's expressed genes and then transport and display this antigenic information on the cell surface. This allows CD8 T cells to identify pathological cells that are synthesizing abnormal proteins, such as cancers that are expressing mutated proteins. In order for many cancers to arise and progress, they need to evolve mechanisms to avoid elimination by CD8 T cells. MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM ...


A Novel Dna And Protein Combination Covid-19 Vaccine Formulation Provides Full Protection Against Sars-Cov-2 In Rhesus Macaques, Yuzhong Li, Guangnan Hu, Shixia Wang, Qihan Li, Shan Lu, Wei Cun 2021 Peking Union Medical College

A Novel Dna And Protein Combination Covid-19 Vaccine Formulation Provides Full Protection Against Sars-Cov-2 In Rhesus Macaques, Yuzhong Li, Guangnan Hu, Shixia Wang, Qihan Li, Shan Lu, Wei Cun

COVID-19 Publications by UMass Chan Authors

The current study aims to develop a safe and highly immunogenic COVID-19 vaccine. The novel combination of a DNA vaccine encoding the full-length Spike (S) protein of SARS-CoV-2 and a recombinant S1 protein vaccine induced high level neutralizing antibody and T cell immune responses in both small and large animal models. More significantly, the co-delivery of DNA and protein components at the same time elicited full protection against intratracheal challenge of SARS-CoV-2 viruses in immunized rhesus macaques. As both DNA and protein vaccines have been proven safe in previous human studies, and DNA vaccines are capable of eliciting germinal center ...


Human Antibody Immune Responses Are Personalized By Selective Removal Of Mhc-Ii Peptide Epitopes [Preprint], Matias Gutiérrez-González, Padma P. Nanaware, Liying Lu, Lawrence J. Stern, Brandon J. DeKosky 2021 University of Kansas

Human Antibody Immune Responses Are Personalized By Selective Removal Of Mhc-Ii Peptide Epitopes [Preprint], Matias Gutiérrez-González, Padma P. Nanaware, Liying Lu, Lawrence J. Stern, Brandon J. Dekosky

University of Massachusetts Medical School Faculty Publications

Human antibody responses are established by the generation of combinatorial sequence diversity in antibody variable domains, followed by iterative rounds of mutation and selection via T cell recognition of antigen peptides presented on MHC-II. Here, we report that MHC-II peptide epitope deletion from B cell receptors (BCRs) correlates with antibody development in vivo. Large-scale antibody sequence analysis and experimental validation of peptide binding revealed that MHC-II epitope removal from BCRs is linked to genetic signatures of T cell help, and donor-specific antibody repertoire modeling demonstrated that somatic hypermutation selectively targets the personalized MHC-II epitopes in antibody variable regions. Mining of ...


T Cells In The Brain Enhance Neonatal Mortality During Peripheral Lcmv Infection, Laurie L. Kenney, Erik P. Carter, Anna Gil, Liisa K. Selin 2021 University of Massachusetts Medical School

T Cells In The Brain Enhance Neonatal Mortality During Peripheral Lcmv Infection, Laurie L. Kenney, Erik P. Carter, Anna Gil, Liisa K. Selin

Open Access Publications by UMass Chan Authors

In adult mice the severity of disease from viral infections is determined by the balance between the efficiency of the immune response and the magnitude of viral load. Here, the impact of this dynamic is examined in neonates. Newborns are highly susceptible to infections due to poor innate responses, lower numbers of T cells and Th2-prone immune responses. Eighty-percent of 7-day old mice, immunologically equivalent to human neonates, succumbed to extremely low doses (5 PFU) of the essentially non-lethal lymphocytic choriomeningitis virus (LCMV-Armstrong) given intraperitoneally. This increased lethality was determined to be dependent upon poor early viral control, as well ...


Tick Extracellular Vesicles Enable Arthropod Feeding And Promote Distinct Outcomes Of Bacterial Infection, Adela S. Oliva Chávez, Xiaowei Wang, Liron Marnin, Nathan K. Archer, Holly L. Hammond, Erin E. McClure Carroll, Dana K. Shaw, Brenden G. Tully, Amanda D. Buskirk, Shelby L. Ford, L. Rainer Butler, Preeti Shahi, Kateryna Morozova, Cristina C. Clement, Lauren Lawres, Anya J. O'Neal, Choukri Ben Mamoun, Kathleen L. Mason, Brandi E. Hobbs, Glen A. Scoles, Eileen M. Barry, Daniel E. Sonenshine, Utpal Pal, Jesus G. Valenzuela, Marcelo B. Sztein, Marcela F. Pasetti, Michael L. Levin, Michail Kotsyfakis, Steven M. Jay, Jason F. Huntley, Lloyd S. Miller, Laura Santambrogio, Joao H.F. Pedra 2021 Old Dominion University

Tick Extracellular Vesicles Enable Arthropod Feeding And Promote Distinct Outcomes Of Bacterial Infection, Adela S. Oliva Chávez, Xiaowei Wang, Liron Marnin, Nathan K. Archer, Holly L. Hammond, Erin E. Mcclure Carroll, Dana K. Shaw, Brenden G. Tully, Amanda D. Buskirk, Shelby L. Ford, L. Rainer Butler, Preeti Shahi, Kateryna Morozova, Cristina C. Clement, Lauren Lawres, Anya J. O'Neal, Choukri Ben Mamoun, Kathleen L. Mason, Brandi E. Hobbs, Glen A. Scoles, Eileen M. Barry, Daniel E. Sonenshine, Utpal Pal, Jesus G. Valenzuela, Marcelo B. Sztein, Marcela F. Pasetti, Michael L. Levin, Michail Kotsyfakis, Steven M. Jay, Jason F. Huntley, Lloyd S. Miller, Laura Santambrogio, Joao H.F. Pedra

Biological Sciences Faculty Publications

Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on ...


Sars-Cov-2 Receptors Are Expressed On Human Platelets And The Effect Of Aspirin On Clinical Outcomes In Covid-19 Patients [Preprint], Aditya Sahai, Milka Koupenova-Zamor, Jane E. Freedman, Scott Cameron 2020 Case Western Reserve University

Sars-Cov-2 Receptors Are Expressed On Human Platelets And The Effect Of Aspirin On Clinical Outcomes In Covid-19 Patients [Preprint], Aditya Sahai, Milka Koupenova-Zamor, Jane E. Freedman, Scott Cameron

COVID-19 Publications by UMass Chan Authors

Coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic events. However, the role of platelets in the elevated observed thrombotic risk in COVID-19 and utility of anti-platelet agents in attenuating thrombosis is unknown. We aimed to determine if human platelets express the known SARS-CoV-2 receptor-protease axis on their cell surface and assess whether the anti-platelet effect of aspirin may mitigate risk of myocardial infarction (MI), cerebrovascular accident (CVA), and venous thromboembolism (VTE) in COVID-19. Expression of ACE2 and TMPRSS2 on human platelets were detected by immunoblotting and confirmed by confocal microscopy. We ...


The Long Non-Coding Rna Lucat1 Is A Negative Feedback Regulator Of Interferon Responses In Humans, Shiuli Agarwal, Tim Vierbuchen, Sreya Ghosh, Jennie Chan, Zhaozhao Jiang, Richard K. Kandasamy, Emiliano Ricci, Katherine A. Fitzgerald 2020 University of Massachusetts Medical School

The Long Non-Coding Rna Lucat1 Is A Negative Feedback Regulator Of Interferon Responses In Humans, Shiuli Agarwal, Tim Vierbuchen, Sreya Ghosh, Jennie Chan, Zhaozhao Jiang, Richard K. Kandasamy, Emiliano Ricci, Katherine A. Fitzgerald

Open Access Publications by UMass Chan Authors

Long non-coding RNAs are important regulators of biological processes including immune responses. The immunoregulatory functions of lncRNAs have been revealed primarily in murine models with limited understanding of lncRNAs in human immune responses. Here, we identify lncRNA LUCAT1 which is upregulated in human myeloid cells stimulated with lipopolysaccharide and other innate immune stimuli. Targeted deletion of LUCAT1 in myeloid cells increases expression of type I interferon stimulated genes in response to LPS. By contrast, increased LUCAT1 expression results in a reduction of the inducible ISG response. In activated cells, LUCAT1 is enriched in the nucleus where it associates with chromatin ...


Neutrophil Infiltration Regulates Clock-Gene Expression To Organize Daily Hepatic Metabolism, Maria Crespo, Norman J. Kennedy, Roger J. Davis, Nuria Matesanz, Magdalena Leiva, Guadalupe Sabio 2020 Spanish National Cardiovascular Research Centre

Neutrophil Infiltration Regulates Clock-Gene Expression To Organize Daily Hepatic Metabolism, Maria Crespo, Norman J. Kennedy, Roger J. Davis, Nuria Matesanz, Magdalena Leiva, Guadalupe Sabio

University of Massachusetts Medical School Faculty Publications

Liver metabolism follows diurnal fluctuations through the modulation of molecular clock genes. Disruption of this molecular clock can result in metabolic disease but its potential regulation by immune cells remains unexplored. Here, we demonstrated that in steady state, neutrophils infiltrated the mouse liver following a circadian pattern and regulated hepatocyte clock-genes by neutrophil elastase (NE) secretion. NE signals through c-Jun NH2-terminal kinase (JNK) inhibiting fibroblast growth factor 21 (FGF21) and activating Bmal1 expression in the hepatocyte. Interestingly, mice with neutropenia, defective neutrophil infiltration or lacking elastase were protected against steatosis correlating with lower JNK activation, reduced Bmal1 and increased FGF21 ...


Changes In Selected Haematological Parameters Associated With Jak1/Jak2 Inhibition Observed In Patients With Rheumatoid Arthritis Treated With Baricitinib, Jonathan Kay, Masayoshi Harigai, Josh Rancourt, Christina Dickson, Thomas Melby, Maher Issa, Inmaculada de la Torre, Yoshitaka Isaka, Anabela Cardoso, Chadi Saifan, Edward C. Keystone, Ronald F. van Vollenhoven, Jon T. Giles, Tom Wj. Huizinga, Joel M. Kremer 2020 University of Massachusetts Medical School

Changes In Selected Haematological Parameters Associated With Jak1/Jak2 Inhibition Observed In Patients With Rheumatoid Arthritis Treated With Baricitinib, Jonathan Kay, Masayoshi Harigai, Josh Rancourt, Christina Dickson, Thomas Melby, Maher Issa, Inmaculada De La Torre, Yoshitaka Isaka, Anabela Cardoso, Chadi Saifan, Edward C. Keystone, Ronald F. Van Vollenhoven, Jon T. Giles, Tom Wj. Huizinga, Joel M. Kremer

Open Access Publications by UMass Chan Authors

OBJECTIVE: To characterise changes in selected haematological parameters following once-daily oral baricitinib dosing.

METHODS: Data were pooled from eight randomised clinical trials (four phase 3, three phase 2, one phase 1b) and one long-term extension. Changes in haematological parameters were evaluated up to 128 weeks (N=2387); overall safety of baricitinib was assessed up to 6 years (N=3492).

RESULTS: Mean absolute neutrophil counts decreased (-1.36x10(9)/L) within 1 month, followed by stabilisation within the normal reference range through week 128. The incidence of serious infections was not elevated in patients with neutropenia during the 24-week placebo-controlled period ...


Extracellular Micrornas In Human Circulation Are Associated With Mirisc Complexes That Are Accessible To Anti-Ago2 Antibody And Can Bind Target Mimic Oligonucleotides, Hirosha Geekiyanage, Shima Rayatpisheh, James A. Wohlschlegel, Robert H. Brown Jr., Victor R. Ambros 2020 University of Massachusetts Medical School

Extracellular Micrornas In Human Circulation Are Associated With Mirisc Complexes That Are Accessible To Anti-Ago2 Antibody And Can Bind Target Mimic Oligonucleotides, Hirosha Geekiyanage, Shima Rayatpisheh, James A. Wohlschlegel, Robert H. Brown Jr., Victor R. Ambros

Open Access Publications by UMass Chan Authors

MicroRNAs (miRNAs) function cell-intrinsically to regulate gene expression by base-pairing to complementary mRNA targets while in association with Argonaute, the effector protein of the miRNA-mediated silencing complex (miRISC). A relatively dilute population of miRNAs can be found extracellularly in body fluids such as human blood plasma and cerebrospinal fluid (CSF). The remarkable stability of circulating miRNAs in such harsh extracellular environments can be attributed to their association with protective macromolecular complexes, including extracellular vesicles (EVs), proteins such as Argonaut 2 (AGO2), or high-density lipoproteins. The precise origins and the potential biological significance of various forms of miRNA-containing extracellular complexes are ...


Caspase-8 Mediates Inflammation And Disease In Rodent Malaria, Larissa M. N. Pereira, Patricia Aparecida Assis, Natalia M. de Araujo, Danielle Fernandes Durso, Caroline Junqueira, Marco Antonio Ataide, Dhelio B. Pereira, Egil Lien, Katherine A. Fitzgerald, Dario S. Zamboni, Douglas T. Golenbock, Ricardo T. Gazzinelli 2020 University of Massachusetts Medical School

Caspase-8 Mediates Inflammation And Disease In Rodent Malaria, Larissa M. N. Pereira, Patricia Aparecida Assis, Natalia M. De Araujo, Danielle Fernandes Durso, Caroline Junqueira, Marco Antonio Ataide, Dhelio B. Pereira, Egil Lien, Katherine A. Fitzgerald, Dario S. Zamboni, Douglas T. Golenbock, Ricardo T. Gazzinelli

Open Access Publications by UMass Chan Authors

Earlier studies indicate that either the canonical or non-canonical pathways of inflammasome activation have a limited role on malaria pathogenesis. Here, we report that caspase-8 is a central mediator of systemic inflammation, septic shock in the Plasmodium chabaudi-infected mice and the P. berghei-induced experimental cerebral malaria (ECM). Importantly, our results indicate that the combined deficiencies of caspases-8/1/11 or caspase-8/gasdermin-D (GSDM-D) renders mice impaired to produce both TNFalpha and IL-1beta and highly resistant to lethality in these models, disclosing a complementary, but independent role of caspase-8 and caspases-1/11/GSDM-D in the pathogenesis of malaria. Further, we find ...


Contributions Of Ifn-Gamma And Granulysin To The Clearance Of Plasmodium Yoelii Blood Stage, Natalia Satchiko Hojo-Souza, Patrick Orestes de Azevedo, Julia Teixeira de Castro, Andrea Teixeira-Carvalho, Judy Lieberman, Caroline Junqueira, Ricardo T. Gazzinelli 2020 Oswaldo Cruz Foundation

Contributions Of Ifn-Gamma And Granulysin To The Clearance Of Plasmodium Yoelii Blood Stage, Natalia Satchiko Hojo-Souza, Patrick Orestes De Azevedo, Julia Teixeira De Castro, Andrea Teixeira-Carvalho, Judy Lieberman, Caroline Junqueira, Ricardo T. Gazzinelli

Open Access Publications by UMass Chan Authors

P. vivax-infected Retics (iRetics) express human leukocyte antigen class I (HLA-I), are recognized by CD8+ T cells and killed by granulysin (GNLY) and granzymes. However, how Plasmodium infection induces MHC-I expression on Retics is unknown. In addition, whether GNLY helps control Plasmodium infection in vivo has not been studied. Here, we examine these questions using rodent infection with the P. yoelii 17XNL strain, which has tropism for Retics. Infection with P. yoelii caused extramedullary erythropoiesis, reticulocytosis and expansion of CD8+CD44+CD62L- IFN-gamma-producing T cells that form immune synapses with iRetics. We now provide evidence that MHC-I expression by iRetic ...


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