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Host Immunity Increases Mycobacterium Tuberculosis Reliance On Cytochrome Bd Oxidase, Yi Cai, Eleni Jaecklein, Jared Mackenzie, Kadamba Papavinasasundaram, Michigan State University, Xinchun Chen, Africa Health Research Institute, Christopher M. Sassetti 2020 Shenzhen University

Host Immunity Increases Mycobacterium Tuberculosis Reliance On Cytochrome Bd Oxidase, Yi Cai, Eleni Jaecklein, Jared Mackenzie, Kadamba Papavinasasundaram, Michigan State University, Xinchun Chen, Africa Health Research Institute, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

In order to sustain a persistent infection, Mycobacterium tuberculosis (Mtb) must adapt to a changing environment that is shaped by the developing immune response. This necessity to adapt is evident in the flexibility of many aspects of Mtb metabolism, including a respiratory chain that consists of two distinct terminal cytochrome oxidase complexes. Under the conditions tested thus far, the bc1/aa3 complex appears to play a dominant role, while the alternative bd oxidase is largely redundant. However, presence of two terminal oxidases in this obligate pathogen implies that respiratory requirements might change during infection. We report that the ...


A Cross-Reactive Human Iga Monoclonal Antibody Blocks Sars-Cov-2 Spike-Ace2 Interaction, Ejemel Monir, Qi Li, Shurong Hou, Zachary Schiller, Aaron Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Jacqueline R. Toomey, Ryan Schneider, Anudeep S. Ramchetty, Chandrashekar Ganesa, Lisa Cavacini, Mark S. Klempner, Celia A. Schiffer, Yan Wang 2020 University of Massachusetts Medical School

A Cross-Reactive Human Iga Monoclonal Antibody Blocks Sars-Cov-2 Spike-Ace2 Interaction, Ejemel Monir, Qi Li, Shurong Hou, Zachary Schiller, Aaron Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Jacqueline R. Toomey, Ryan Schneider, Anudeep S. Ramchetty, Chandrashekar Ganesa, Lisa Cavacini, Mark S. Klempner, Celia A. Schiffer, Yan Wang

COVID-19 Publications by UMMS Authors

COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 ...


Mycobacterium Tuberculosis Evasion Of Guanylate Binding Protein-Mediated Host Defense In Mice Requires The Esx1 Secretion System, Andrew J. Olive, Clare M. Smith, Christina E. Baer, Jörn Coers, Christopher M. Sassetti 2020 Michigan State University

Mycobacterium Tuberculosis Evasion Of Guanylate Binding Protein-Mediated Host Defense In Mice Requires The Esx1 Secretion System, Andrew J. Olive, Clare M. Smith, Christina E. Baer, Jörn Coers, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

Cell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis (Mtb) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent inducer of cell-autonomous immunity is the lymphocyte-derived cytokine IFNγ. While the production of IFNγ by T cells is essential to protect against Mtb, it is not capable of fully eradicating Mtb infection. This suggests that Mtb evades a subset of IFNγ-mediated antimicrobial responses, yet what mechanisms Mtb resists remains unclear. The IFNγ-inducible Guanylate binding proteins (GBPs) are key host defense proteins able to control infections with intracellular pathogens. GBPs were previously shown ...


Host Immunity And The Colon Microbiota Of Mice Infected With Citrobacter Rodentium Are Beneficially Modulated By Lipid-Soluble Extract From Late-Cutting Alfalfa In The Early Stages Of Infection, Krysten Fries-Craft, Justin M. Anast, Stephan Schmitz-Esser, Elizabeth A. Bobeck 2020 Iowa State University

Host Immunity And The Colon Microbiota Of Mice Infected With Citrobacter Rodentium Are Beneficially Modulated By Lipid-Soluble Extract From Late-Cutting Alfalfa In The Early Stages Of Infection, Krysten Fries-Craft, Justin M. Anast, Stephan Schmitz-Esser, Elizabeth A. Bobeck

Animal Science Publications

Alfalfa is a forage legume commonly associated with ruminant livestock production that may be a potential source of health-promoting phytochemicals. Anecdotal evidence from producers suggests that later cuttings of alfalfa may be more beneficial to non-ruminants; however, published literature varies greatly in measured outcomes, supplement form, and cutting. The objective of this study was to measure body weight, average daily feed intake, host immunity, and the colon microbiota composition in mice fed hay, aqueous, and chloroform extracts of early (1st) and late (5th) cutting alfalfa before and after challenge with Citrobacter rodentium. Prior to inoculation, alfalfa supplementation did not have ...


Hem1 Deficiency Disrupts Mtorc2 And F-Actin Control In Inherited Immunodysregulatory Disease, Sarah A. Cook, William A. Comrie, Morgan Similuk, Andrew J. Oler, Aiman J. Faruqi, Sheng Yang, D. Eric Anderson, Susan Price, Margery Smelkinson, Baoyu Chen, V. Koneti Rao, Michael J. Lenardo, et al. 2020 National Institutes of Health

Hem1 Deficiency Disrupts Mtorc2 And F-Actin Control In Inherited Immunodysregulatory Disease, Sarah A. Cook, William A. Comrie, Morgan Similuk, Andrew J. Oler, Aiman J. Faruqi, Sheng Yang, D. Eric Anderson, Susan Price, Margery Smelkinson, Baoyu Chen, V. Koneti Rao, Michael J. Lenardo, Et Al.

Biochemistry, Biophysics and Molecular Biology Publications

Immunodeficiency often coincides with hyperactive immune disorders such as autoimmunity, lymphoproliferation, or atopy, but this coincidence is rarely understood on a molecular level. We describe five patients from four families with immunodeficiency coupled with atopy, lymphoproliferation, and cytokine overproduction harboring mutations in NCKAP1L, which encodes the hematopoietic-specific HEM1 protein. These mutations cause the loss of the HEM1 protein and the WAVE regulatory complex (WRC) or disrupt binding to the WRC regulator, Arf1, thereby impairing actin polymerization, synapse formation, and immune cell migration. Diminished cortical actin networks caused by WRC loss led to uncontrolled cytokine release and immune hyperresponsiveness. HEM1 loss ...


Cd11chi Monocyte-Derived Macrophages Are A Major Cellular Compartment Infected By Mycobacterium Tuberculosis, Jinhee Lee, Shayla Boyce, Jennifer Powers, Christina E. Baer, Christopher M. Sassetti, Samuel M. Behar 2020 University of Massachusetts Medical School

Cd11chi Monocyte-Derived Macrophages Are A Major Cellular Compartment Infected By Mycobacterium Tuberculosis, Jinhee Lee, Shayla Boyce, Jennifer Powers, Christina E. Baer, Christopher M. Sassetti, Samuel M. Behar

Open Access Articles

During tuberculosis, lung myeloid cells have two opposing roles: they are an intracellular niche occupied by Mycobacterium tuberculosis, and they restrict bacterial replication. Lung myeloid cells from mice infected with yellow-fluorescent protein expressing M. tuberculosis were analyzed by flow cytometry and transcriptional profiling to identify the cell types infected and their response to infection. CD14, CD38, and Abca1 were expressed more highly by infected alveolar macrophages and CD11cHi monocyte-derived cells compared to uninfected cells. CD14, CD38, and Abca1 "triple positive" (TP) cells had not only the highest infection rates and bacterial loads, but also a strong interferon-gamma signature and nitric ...


Quercetin And Vitamin C: An Experimental, Synergistic Therapy For The Prevention And Treatment Of Sars-Cov-2 Related Disease (Covid-19), Ruben Manuel Luciano Colunga Biancatelli, Max Berrill, John D. Catravas, Paul Ellis Marik 2020 Old Dominion University

Quercetin And Vitamin C: An Experimental, Synergistic Therapy For The Prevention And Treatment Of Sars-Cov-2 Related Disease (Covid-19), Ruben Manuel Luciano Colunga Biancatelli, Max Berrill, John D. Catravas, Paul Ellis Marik

Bioelectrics Publications

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an emergent global threat which is straining worldwide healthcare capacity. As of May 27th, the disease caused by SARS-CoV-2 (COVID-19) has resulted in more than 340,000 deaths worldwide, with 100,000 deaths in the US alone. It is imperative to study and develop pharmacological treatments suitable for the prevention and treatment of COVID-19. Ascorbic acid is a crucial vitamin necessary for the correct functioning of the immune system. It plays a role in stress response and has shown promising results when administered to the critically ill. Quercetin is a well-known flavonoid whose ...


Modeling Vaccination Strategies To Control White-Nose Syndrome In Little Brown Bat Colonies, Eva Cornwell, David Elzinga, Shelby R. Stowe, Alex Capaldi 2020 St. Olaf College

Modeling Vaccination Strategies To Control White-Nose Syndrome In Little Brown Bat Colonies, Eva Cornwell, David Elzinga, Shelby R. Stowe, Alex Capaldi

Biology and Medicine Through Mathematics Conference

No abstract provided.


In Silico Mouse Model Of Infection And Immunity, Daniel Jonas, Michael Kirby, Alan R. Schenkel 2020 Colorado State University

In Silico Mouse Model Of Infection And Immunity, Daniel Jonas, Michael Kirby, Alan R. Schenkel

Biology and Medicine Through Mathematics Conference

No abstract provided.


The Relationship Between Glucocorticoids And The Humoral Immune Response To Mycoplasma Gallisepticum Challenges In Eastern Bluebirds, Joshua Smith 2020 University of Mississippi

The Relationship Between Glucocorticoids And The Humoral Immune Response To Mycoplasma Gallisepticum Challenges In Eastern Bluebirds, Joshua Smith

Honors Theses

Numerous studies have examined relationships between adrenal glucocorticoids and the immune system’s ability to fight disease. The relationship can vary, with glucocorticoids having either stimulatory or inhibitory effects. The pathogenic bacterium Mycoplasma gallisepticum (MG) elicits an adaptive immune response in birds, in which B cells produce MG-specific antibodies to fight the infection and prevent reoccurrence. Previous research found that Eastern Bluebirds that produce the most antibodies in response to MG infection also have the highest glucocorticoid levels. This finding led to the current study investigating whether corticosterone, the primary glucocorticoid in birds, stimulates production of antibodies in response to ...


The Role Of The Bps Immunity Repressor In The Regulation Of Pathogenic Mycobacterium Chelonae Gene Expression, Emma Freeman 2020 University of Maine

The Role Of The Bps Immunity Repressor In The Regulation Of Pathogenic Mycobacterium Chelonae Gene Expression, Emma Freeman

Honors College

Mycobacterium tuberculosis is the leading cause of death by an infectious disease (MacNeil, 2019). In 2018, 10 million people developed tuberculosis and half a million infections were resistant to antibiotics (WHO, 2019). Nearly all members of the M. tuberculosis complex are lysogens, meaning they carry prophage, or integrated viral genomes within the host genome (Fan et al., 2016). The non-pathogenic vaccine strain (M. bovis Bacillus Calmette–Guérin (BCG)) is the exception, which suggests prophage play a role in virulence (Fan et al., 2016). Because not all prophage encode obvious virulence genes, we hypothesize that prophage impact bacterial virulence by altering ...


How Nutrition Can Help To Fight Against Covid-19 Pandemic, Faseeha Aman, Sadia Masood 2020 Centre of advanced studies in health and Technology, Rawalpindi, Pakistan

How Nutrition Can Help To Fight Against Covid-19 Pandemic, Faseeha Aman, Sadia Masood

Section of Internal Medicine

Currently Covid-19 pandemic is a leading challenge across the globe. It is mandatory to attain and maintain good nutritional status to fight against virus. Nutritional status of individual is affected by several factors such as age, sex, health status, life style and medications. Nutritional status of individuals has been used as resilience towards destabilization during this COVID-19 pandemic. Optimal nutrition and dietary nutrient intake impact the immune system, therefore the only sustainable way to survive in current context is to strengthen the immune system. There is no evidence found that supplement can cure the immune system except Vit C, which ...


Effects Of Individual Orsay Virus Proteins On The Intracellular Pathogen Response Of C. Elegans, Barbara Chen, Jessica N. Sowa 2020 West Chester University of Pennsylvania

Effects Of Individual Orsay Virus Proteins On The Intracellular Pathogen Response Of C. Elegans, Barbara Chen, Jessica N. Sowa

Biology Student Work

In order to cause infection, pathogens must avoid destruction by the host immune system. However, how pathogens evolved to evade host immunity is not fully understood. Mammals have two systems of immunity, innate and adaptive, which are regulated by complex interactions between the two systems. In order to study innate immunity exclusively, the roundworm C. elegans is a useful invertebrate model because it lacks adaptive immunity and the complexities that arise from interactions between the two types of immunity. The goal of this project is to investigate whether the individual expression of the Orsay virus capsid and delta-fusion proteins can ...


Identifying Novel Triggers Of The Intracellular Pathogen Response (Ipr) In C. Elegans, Catherine T. Byrnes, Jessica N. Sowa 2020 West Chester University of Pennsylvania

Identifying Novel Triggers Of The Intracellular Pathogen Response (Ipr) In C. Elegans, Catherine T. Byrnes, Jessica N. Sowa

Biology Student Work

The intracellular pathogen response (IPR) is a cell signaling pathway found in C. elegans that is triggered when pathogenic microorganisms invade, and immune responses attempt to eliminate the threat. Due to the relative simplicity of C. elegans, they are an excellent model organism to analyze the cell signaling pathways triggered by various pathogens. They lack the complex immune systems of larger organisms, making it easier to study the involved cell signaling pathways. Past studies have shown that the IPR can also be triggered via intestinal wounding. Heat stress, viral infection, and proteasome stress are all known triggers of the IPR ...


Innate Immunity In The C. Elegans Intestine Is Programmed By A Neuronal Regulator Of Awc Olfactory Neuron Development, Kyle J. Foster, Hilary K. Cheesman, Pengpeng Liu, Nicholas D. Peterson, Sarah M. Anderson, Read Pukkila-Worley 2020 University of Massachusetts Medical School

Innate Immunity In The C. Elegans Intestine Is Programmed By A Neuronal Regulator Of Awc Olfactory Neuron Development, Kyle J. Foster, Hilary K. Cheesman, Pengpeng Liu, Nicholas D. Peterson, Sarah M. Anderson, Read Pukkila-Worley

Open Access Articles

Olfactory neurons allow animals to discriminate nutritious food sources from potential pathogens. From a forward genetic screen, we uncovered a surprising requirement for the olfactory neuron gene olrn-1 in the regulation of intestinal epithelial immunity in Caenorhabditis elegans. During nematode development, olrn-1 is required to program the expression of odorant receptors in the AWC olfactory neuron pair. Here, we show that olrn-1 also functions in AWC neurons in the cell non-autonomous suppression of the canonical p38 MAPK PMK-1 immune pathway in the intestine. Low activity of OLRN-1, which activates the p38 MAPK signaling cassette in AWC neurons during larval development ...


Development Of An Attenuated Zika Virus By Editing The 5’ Untranslated Region, E. Ashley Thompson 2020 The University of Southern Mississippi

Development Of An Attenuated Zika Virus By Editing The 5’ Untranslated Region, E. Ashley Thompson

Master's Theses

Zika Virus (ZIKV) is a mosquito-transmitted flavivirus that usually causes no symptoms to mild febrile in humans, and it has been regarded as an insignificant pathogen to public health. However, recent outbreaks of ZIKV infection have revealed that ZIKV can cause severe neurological effects in adults, such as Guillain-Barre Syndrome (GBS), and in infants whose mothers acquired the virus during pregnancy, causing Congenital Zika Syndrome (CZS). Currently, no approved vaccine is available and there is a critical need to develop an effective and safe vaccine. While most vaccine developmental strategies target the viral prM-E protein of ZIKV, we aimed to ...


A Systematic Re-Examination Of Processing Of Mhci-Bound Antigenic Peptide Precursors By Er Aminopeptidase 1, George Mavridis, Richa Arya, Alexander Domnick, Jerome Zoidakis, Manousos Makridakis, Antonia Vlahou, Anastasia Mpakali, Angelos Lelis, Dimitris Georgiadis, Robert Tampe, Athanasios Papakyriakou, Lawrence J. Stern, Efstratios Stratikos 2020 National Center for Scientific Research Demokritos

A Systematic Re-Examination Of Processing Of Mhci-Bound Antigenic Peptide Precursors By Er Aminopeptidase 1, George Mavridis, Richa Arya, Alexander Domnick, Jerome Zoidakis, Manousos Makridakis, Antonia Vlahou, Anastasia Mpakali, Angelos Lelis, Dimitris Georgiadis, Robert Tampe, Athanasios Papakyriakou, Lawrence J. Stern, Efstratios Stratikos

Open Access Articles

Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims antigenic peptide precursors to generate mature antigenic peptides for presentation by major histocompatibility complex class I (MHCI) molecules and regulates adaptive immune responses. ERAP1 has been proposed to trim peptide precursors both in solution and in pre-formed MHCI-peptide complexes, but which mode is more relevant to its biological function remains controversial. Here, we compared ERAP1-mediated trimming of antigenic peptide precursors in solution or when bound to three MHCI alleles, HLA-B*58, HLA-B*08 and HLA-A*02. For all MHCI-peptide combinations, peptide binding onto MHCI protected against ERAP1-mediated trimming. In only a single MHCI-peptide combination ...


Natural Polymorphism Of Mycobacterium Tuberculosis And Cd8 T Cell Immunity, Rujapak Sutiwisesak 2020 University of Massachusetts Medical School

Natural Polymorphism Of Mycobacterium Tuberculosis And Cd8 T Cell Immunity, Rujapak Sutiwisesak

GSBS Dissertations and Theses

Coevolution between Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, and the human host has been documented for thousands of years. Interestingly, while T cell immunity is crucial for host protection and survival, T cell antigens are the most conserved region of the Mtb genome. Hypothetically, Mtb adapts under immune pressure to exploit T cell responses for its benefit from inflammation and tissue destruction for ultimately transmission.

EsxH, a gene encoding immunodominant TB10.4 protein, however, contains polymorphic regions corresponding to T cell epitopes. Here, I present two complementary analyses to examine how Mtb modulates TB10.4 for immune evasion ...


Neonatal-Derived Il-17 Producing Dermal Gammadelta T Cells Are Required To Prevent Spontaneous Atopic Dermatitis, Nicholas A. Spidale, Nidhi Malhotra, Michela Frascoli, Katelyn E. Sylvia, Bing Miu, Coral Freeman, Brian D. Stadinski, Eric Huseby, Joonso Kang 2020 University of Massachusetts Medical School

Neonatal-Derived Il-17 Producing Dermal Gammadelta T Cells Are Required To Prevent Spontaneous Atopic Dermatitis, Nicholas A. Spidale, Nidhi Malhotra, Michela Frascoli, Katelyn E. Sylvia, Bing Miu, Coral Freeman, Brian D. Stadinski, Eric Huseby, Joonso Kang

Open Access Articles

Atopic Dermatitis (AD) is a T cell-mediated chronic skin disease and is associated with altered skin barrier integrity. Infants with mutations in genes involved in tissue barrier fitness are predisposed towards inflammatory diseases, but most do not develop or sustain the diseases, suggesting that there exist regulatory immune mechanisms to prevent aberrant inflammation. The absence of one single murine dermal cell type, the innate neonatal-derived IL-17 producing gammadelta T (Tgammadelta17) cells, from birth resulted in spontaneous, highly penetrant AD with many of the major hallmarks of human AD. In Tgammadelta17 cell-deficient mice, basal keratinocyte transcriptome was altered months in advance ...


Long Non-Coding Rna Lincrna-Eps Inhibits Host Defense Against Listeria Monocytogenes Infection, Federica Agliano, Katherine A. Fitzgerald, Anthony T. Vella, Vijay A. Rathinam, Andrei E. Medvedev 2020 University of Connecticut

Long Non-Coding Rna Lincrna-Eps Inhibits Host Defense Against Listeria Monocytogenes Infection, Federica Agliano, Katherine A. Fitzgerald, Anthony T. Vella, Vijay A. Rathinam, Andrei E. Medvedev

Open Access Articles

Long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in several biological systems. The long intergenic RNA-erythroid pro-survival (lincRNA-EPS) has been shown to play a critical role in restraining inflammatory gene expression. However, the function of lincRNA-EPS during bacterial infections remains unknown. Here, we demonstrate that following infection with the intracellular bacterium Listeria monocytogenes, both mouse macrophages and dendritic cells lacking lincRNA-EPS exhibit an enhanced expression of proinflammatory cytokine genes, as well as an increased expression of the inducible nitric oxide synthase (iNos) and nitric oxide (NO) production. Importantly, we found that lincRNA-EPS(-/-) mice intraperitoneally infected with ...


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