Digital Commons Network^™

Optimal Timing Of Antiretroviral Therapy Initiation In Children And Adolescents With Human Immunodeficiency Virus-Associated Pulmonary Tuberculosis, Alexander Kay, Jose Mendez-Reyes, Tara Devezin, Meenakshi Bakaya, Teresa Steffy, Sandile Dlamini, Amos Msekandiana, Tara Ness, Jason Bacha, Pauline Amuge, Mogomotsi Matshaba, Moses Chodota, Phoebe Nyasulu, Lineo Thahane, Lumumbwa Mwita, Adeodata Kekitiinwa, Andrew Dinardo, Bhekumusa Lukhele, H Lester Kirchner, Anna Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: There is insufficient evidence in children and adolescents with human immunodeficiency virus (CAHIV) to guide the timing of antiretroviral treatment (ART) initiation after starting treatment for pulmonary tuberculosis (pTB). To address this knowledge gap, we evaluated the risk of mortality associated with timing of ART initiation in ART-naive CAHIV treated for pTB.

METHODS: Data were extracted from electronic medical records of ART-naive patients, aged 0-19 years, who were treated for HIV-associated pTB at Baylor Centers of Excellence in Botswana, Eswatini, Malawi, Lesotho, Tanzania, or Uganda between 2013 and 2020. Data were analyzed against a primary outcome of all-cause mortality …

Inherited Human Itk Deficiency Impairs Ifn-Γ Immunity And Underlies Tuberculosis, Masato Ogishi, Rui Yang, Rémy Rodriguez, Dominic P Golec, Emmanuel Martin, Quentin Philippot, Jonathan Bohlen, Simon J Pelham, Andrés Augusto Arias, Taushif Khan, Manar Ata, Fatima Al Ali, Flore Rozenberg, Xiao-Fei Kong, Maya Chrabieh, Candice Laine, Wei-Te Lei, Ji Eun Han, Yoann Seeleuthner, Zenia Kaul, Emmanuelle Jouanguy, Vivien Béziat, Leila Youssefian, Hassan Vahidnezhad, V Koneti Rao, Bénédicte Neven, Claire Fieschi, Davood Mansouri, Mohammad Shahrooei, Sevgi Pekcan, Gulsum Alkan, Melike Emiroğlu, Hüseyin Tokgöz, Jouni Uitto, Fabian Hauck, Jacinta Bustamante, Laurent Abel, Sevgi Keles, Nima Parvaneh, Nico Marr, Pamela L Schwartzberg, Sylvain Latour, Jean-Laurent Casanova, Stéphanie Boisson-Dupuis

Department of Dermatology and Cutaneous Biology Faculty Papers

Inborn errors of IFN-γ immunity can underlie tuberculosis (TB). We report three patients from two kindreds without EBV viremia or disease but with severe TB and inherited complete ITK deficiency, a condition associated with severe EBV disease that renders immunological studies challenging. They have CD4+ αβ T lymphocytopenia with a concomitant expansion of CD4-CD8- double-negative (DN) αβ and Vδ2- γδ T lymphocytes, both displaying a unique CD38+CD45RA+T-bet+EOMES- phenotype. Itk-deficient mice recapitulated an expansion of the γδ T and DN αβ T lymphocyte populations in the thymus and spleen, respectively. Moreover, the patients' T lymphocytes secrete small amounts of IFN-γ in …

The Covid-19 Pandemic As A Catalyst For Integrated Global Mental Healthcare And Tuberculosis Care, Alexander L. Chu, Aneeta Pasha, Carmen Contreras, Leonid Lecca, Annika C. Sweetland, Jerome T. Galea

Social Work Faculty Publications

Mental disorders are common among persons with tuberculosis (TB), and the COVID-19 pandemic has only amplified the mental and physical health consequences of this deadly synergy. Here, we call to attention the immense vulnerability of people with TB to mental disorders during the pandemic and highlight the unique challenges and opportunities that the pandemic brings to the future integration of global TB and mental healthcare. We argue that the pandemic era is an ideal period to accelerate this integration and we provide research and policy recommendations to actualise this urgent need.

Relationship Between Homelessness, Substance Use, Employment, Living On A Reservation And Tuberculosis Among Northern Plains Native Americans, Darla Mccloskey

Walden Dissertations and Doctoral Studies

Native Americans in the Northern Plains have a long history of tuberculosis (TB) infections. There is limited research on the causes of latent TB infections (LTBI) and TB in this population. The purpose of this quantitative study was to assess the relationship between latent TB and factors of homelessness, substance use, employment, living on a reservation, and active or latent TB among this population using the eco-social theory as the theoretical framework. Data from 146 TB cases of Native Americans living in the Northern Plains and diagnosed with TB from 1999 to 2019 were analyzed using chi-square tests that showed …

Case Series; Imaging In Lesser-Known Ailments Of The Pituitary Gland And Sellar Region, Harisha H L, Kavya Bhadrapura Thimmegowda, Ajay Hanumanthu, Vikram Patil Dr, Gurumurthy B, Dr Abhijith Roys

Digital Journal of Clinical Medicine

No abstract provided.

Relationship Between Homelessness, Substance Use, Employment, Living On A Reservation And Tuberculosis Among Northern Plains Native Americans, Darla Mccloskey

Walden Dissertations and Doctoral Studies

Native Americans in the Northern Plains have a long history of tuberculosis (TB) infections. There is limited research on the causes of latent TB infections (LTBI) and TB in this population. The purpose of this quantitative study was to assess the relationship between latent TB and factors of homelessness, substance use, employment, living on a reservation, and active or latent TB among this population using the eco-social theory as the theoretical framework. Data from 146 TB cases of Native Americans living in the Northern Plains and diagnosed with TB from 1999 to 2019 were analyzed using chi-square tests that showed …

Il-27 Negatively Impacts Immunity Developed Following Bcg Administration, Shelby D. Bradford

Graduate Theses, Dissertations, and Problem Reports (ETD)

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a predominantly respiratory pathogen responsible for over ten million infections and one million deaths last year. Despite it being a primary objective of the World Health Organization (WHO) for several decades to irradicate TB, progress toward this objective has fallen short of the 2020 target to end TB by 2035. Meeting this goal will require advancements in diagnostic tools, education, healthcare access, and treatments and preventatives. Regarding prevention, the primary tool for this strategy is through vaccination. Currently, the only licensed vaccine for protection against TB is the century old …

Is It Tuberculosis Mastitis Or Granulomatous Mastitis? A Thirteen-Year Experience At A University Hospital, Handan İnönü Köseoğlu, Mehmet Fati̇h Daşiran, Reşi̇t Doğan Köseoğlu, Zeki̇ye Ruken Yüksekkaya Çeli̇kyay, Mehmet Berati̇ Kaleli̇oğlu

Turkish Journal of Medical Sciences

Background/aim: Granulomatous mastitis (GM) is a rare inflammatory disease of the breast. Tuberculosis mastitis (TM), one of the causes of GM, is a rare form of extrapulmonary tuberculosis. The clinical, radiological, and histopathological findings of TM and GM are similar, and sometimes it is difficult to make a distinction between these disease states. In this study, we aimed to evaluate the clinical and radiological features, diagnostic techniques, treatment modalities and treatment outcomes of the patients with GM and TM. Materials and methods: The data of the patients with confirmed GM by histopathologic examination of biopsy specimens between 2007 and 2020 …

Factors Associated With Prevalent Mycobacterium Tuberculosis Infection And Disease Among Adolescents And Adults Exposed To Rifampin-Resistant Tuberculosis In The Household, Soyeon Kim, Anneke C. Hesseling, Xingye Wu, Michael D. Hughes, N. Sarita Shah, Sanjay Gaikwad, Nishi Kumarasamy, Erika Mitchell, Mey Leon, Pedro Gonzales, Sharlaa Badal-Faesen, Madeleine Lourens, Sandy Nerette, Justin Shenje, Petra De Koker, Supalert Nedsuwan, Lerato Mohapi, Unoda A. Chakalisa, Rosie Mngqbisa, Rodrigo Otávio Da Silva Escada, Samuel Ouma, Barbara Heckman, Linda Naini, Amita Gupta, Susan Swindells, Gavin Churchyard, Actg A5300/Impaact 2003 Phoenix Feasibility Study Team

Journal Articles: Infectious Diseases

BACKGROUND: Understanding factors associated with prevalent Mycobacterium tuberculosis infection and prevalent TB disease in household contacts of patients with drug-resistant tuberculosis (TB) may be useful for TB program staff conducting contact investigations.

METHODS: Using data from a cross-sectional study that enrolled index participants with rifampin-resistant pulmonary TB and their household contacts (HHCs), we evaluated HHCs age ≥15 years for factors associated with two outcomes: Mycobacterium tuberculosis infection and TB disease. Among HHCs who were not already diagnosed with current active TB disease by the TB program, Mycobacterium tuberculosis infection was determined by interferon-gamma release assay (IGRA). TB disease was adjudicated …

Relationship Between Homelessness, Substance Use, Employment, Living On A Reservation And Tuberculosis Among Northern Plains Native Americans, Darla Mccloskey

Walden Dissertations and Doctoral Studies

Native Americans in the Northern Plains have a long history of tuberculosis (TB) infections. There is limited research on the causes of latent TB infections (LTBI) and TB in this population. The purpose of this quantitative study was to assess the relationship between latent TB and factors of homelessness, substance use, employment, living on a reservation, and active or latent TB among this population using the eco-social theory as the theoretical framework. Data from 146 TB cases of Native Americans living in the Northern Plains and diagnosed with TB from 1999 to 2019 were analyzed using chi-square tests that showed …

Evaluation Of Treatment Regimens And Long-Term Clinical Outcomes In Patients With Isoniazid-Resistant Pulmonary Tuberculosis: A 5-Year Follow-Up, Ayşe Feyza Aslan, Medi̇ha Gönenç Ortaköylü, Belma Akbaba Bağci, Sezer Toprak

Turkish Journal of Medical Sciences

Background/aim: Considering its early bactericidal activity, isoniazid (H) is an important first-line agent in tuberculosis (TB) treatment. The aim of this study was to evaluate the treatment regimens and results of H-resistant pulmonary TB patients. Materials and methods: We retrospectively evaluated treatment regimens and results of 188 H-resistant pulmonary TB patients who were treated in our center between January 2015 and December 2017. Treatment regimens applied were noted and treatment outcomes were recorded. The long-term results were evaluated. Results: Totally 174 (92.6%) of 188 patients with H-resistant pulmonary TB achieved treatment success. Ninety-seven patients (51.6%) were cured and 77 patients …

Diagnostic Accuracy Of Different Cut-Off Values Of Adenosine Deaminase Levels In Tuberculous Pleural Effusion, Kiran Iqbal Masood, Shayan Shahid, Kauser Jabeen, Joveria Farooqi, Sabeika Raza Kerawala, Muhammad Irfan

Department of Pathology and Laboratory Medicine

Objective: To assess the diagnostic accuracy of different cut-off values of pleural fluid adenosine deaminase levels as a diagnostic method for tuberculous pleural effusion.
Method: The prospective study was conducted from 2014 to 2016 at the Aga Khan University Hospital, Karachi, and comprised pleural fluid samples of adult patients with and without tuberculosis which were tested for adenosine deaminase levels, and divided into tuberculosis group A and non-tuberculosis group B. Sensitivity, specificity, negative predictive value and positive predictive value were calculated using different cut-offs. Data was analysed using IBM SPSS (Statistical Package for Social Sciences) version 21.0 (IBM Corp., Armonk, …

The Importance Of Mitral Valve Prolapse Doming Volume In The Assessment Of Left Ventricular Stroke Volume With Cardiac Mri, Brendan K Podell, Omowunmi Aibana, Chuan-Chin Huang, James E Dilisio, Macallister C Harris, David F Ackart, Kody Armann, Alexander Grover, Patrice Severe, Marc Antoine Jean Juste, Kathryn Dupnik, Randall J Basaraba, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Although previous studies have shown that vitamin A deficiency is associated with incident tuberculosis (TB) disease, the direction of the association has not been established. We investigated the impact of vitamin A deficiency on TB disease progression.

METHODS: We conducted a longitudinal cohort study nested within a randomized clinical trial among HIV-infected patients in Haiti. We compared serial vitamin A levels in individuals who developed TB disease to controls matched on age, gender, follow-up time, and time to antiretroviral therapy initiation. We also evaluated histopathology, bacterial load, and immune outcomes in TB infection in a guinea pig model of …

Structural And Inhibitory Studies On (I)Two Mycobacterium Tuberculosis Enzymes Essential For Capsular Glucan Biosynthesis And Mrna Degradation: (Ii) Hantann Virus L-Protein Endonuclease Domain, Hettiarachchige Thilina D. Jayasinghe

Theses & Dissertations

Mycobacterium tuberculosis (Mtb) is the pathogenic bacterium species that causes Tuberculosis (TB). Understanding the major biosynthetic pathways responsible for cell viability is essential in developing new drugs against Mtb. The first two projects will reflect our approach in identifying inhibitors against Mtb GlgE, Mtb GpsI, and characterization of protein inhibitor interactions using X-ray crystallography.

The enzyme GlgE plays an essential role in the α-glucan biosynthesis pathway in Mtb cells. These α-glucans are one of the major structural units in the Mtb capsule. GlgE catalyzes the elongation of α-glucan by transferring maltose from maltose-1-phosphate (M1P) to the non-reducing end …

Structural And Biochemical Studies Of Three Enzymes Involved In Amino Acid Metabolism To Develop Novel Drugs, Yahani Pankaja Jayasinghe Arachchige

Theses & Dissertations

Intrinsic drug resistance in bacteria predates the clinical use of antibiotics. Additionally, heterogeneous metabolic states and the ability of many bacteria to form biofilms further enhances bacterial survival during infection and exacerbates treatment challenges. This necessitates the identification of novel drugs against new drug targets. These studies focus on the development of compounds targeting enzymes in Mycobacterium tuberculosis (Mtb) and Staphylococcus aureus that avoid intrinsic antibiotic defenses. The Mtb-encoded homoserine transacetylase enzyme (HTA) catalyzes the first step of the methionine biosynthesis pathway that produces methionine and S-adenosyl methionine. These compounds are shown to be essential for both dormant …

Differential Role Of Type 2 Diabetes As A Risk Factor For Tuberculosis In The Elderly Versus Younger Adults, Blanca I. Restrepo, Julia M. Scordo, Genesis P. Aguillón-Durán, Doris Ayala, Ana P. Quirino-Cerrillo, Raúl Loera-Salazar, America Cruz-González, Jose A. Caso, Mateo Joya-Ayala, Esperanza M. García-Oropesa, Alejandra B. Salinas

School of Medicine Publications

The elderly are understudied despite their high risk of tuberculosis (TB). We sought to identify factors underlying the lack of an association between TB and type 2 diabetes (T2D) in the elderly, but not adults. We conducted a case–control study in elderly (≥65 years old; ELD) vs. younger adults (young/middle-aged adults (18–44/45–64 years old; YA|MAA) stratified by TB and T2D, using a research study population (n = 1160) and TB surveillance data (n = 8783). In the research study population the adjusted odds ratio (AOR) of TB in T2D was highest in young adults (AOR 6.48) but waned with age …

Managing Tuberculosis In Refugee Populations, Roselyn Fierkens

Senior Honors Theses

Tuberculosis (TB) is an airborne-transmitted infectious disease, responsible for more global deaths than HIV. Multidrug-resistant strains are developing, which heightens the need for swift eradication. Current data states that 71.4% of all TB cases in the United States occur in foreign-born individuals, so populations traveling from TB endemic areas are a key target population for prevention strategies. Various screening procedures exist, but no successful standard is in place. Beyond prevention and treatment strategies, adaptations to cultural communication differences are integral to successful medical interventions. This synthesis of TB pathophysiology, treatments, risk factors, and cultural considerations is intended for use in …

Impact Of Instrumental Support From Family On Medication Adherence Among Tuberculosis Patients, Astuti Yuni Nursasi, Mega Hasanul Huda, Syifa Widya Rahmasari

Kesmas

Instrumental support is concrete and tangible, for instance, helping to provide food or accompanying patients to health care facilities. However, its impact on medication adherence among tuberculosis patients in Indonesia needs to be explored. This study aimed to examine the impact of instrumental support from family on tuberculosis patients’ adherence to medication in Bogor City, West Java Province, Indonesia. A cross-sectional study involving 106 participants with an age average of 39.7 (SD = 14.9) was conducted in 12 primary health care (PHC). The independent variables (age, sex, education, employment status, wealth index, and the distance between home and PHC) of …

High Throughput Sequencing For Clinical Tuberculosis: An Overview, Tara E Ness, Andrew Dinardo, Maha R Farhat

Faculty, Staff and Students Publications

High throughput sequencing (HTS) can identify the presence of Mycobacterium tuberculosis DNA in a clinical sample while also providing information on drug susceptibility. Multiple studies have provided a context for exploring the clinical application of HTS for TB diagnosis. The workflow challenges, strengths and limitations of the various sequencing platforms, and tools used for analysis are presented to provide a framework for further innovations in the field.

A High-Resolution 3d Atlas Of The Spectrum Of Tuberculous Andcovid-19 Lung Lesions, Gordon Wells, Joel N Glasgow, Kievershen Nargan, Kapongo Lumamba, Rajhmun Madansein, Kameel Maharaj, Leon Y Perumal, Malcolm Matthew, Robert L Hunter, Hayden Pacl, Jacelyn E Peabody Lever, Denise D Stanford, Satinder P Singh, Prachi Bajpai, Upender Manne, Paul V Benson, Steven M Rowe, Stephan Le Roux, Alex Sigal, Muofhe Tshibalanganda, Carlyn Wells, Anton Du Plessis, Mpumelelo Msimang, Threnesan Naidoo, Adrie J C Steyn

Faculty, Staff and Student Publications

Our current understanding of the spectrum of TB and COVID-19 lesions in the human lung is limited by a reliance on low-resolution imaging platforms that cannot provide accurate 3D representations of lesion types within the context of the whole lung. To characterize TB and COVID-19 lesions in 3D, we applied micro/nanocomputed tomography to surgically resected, postmortem, and paraffin-embedded human lung tissue. We define a spectrum of TB pathologies, including cavitary lesions, calcium deposits outside and inside necrotic granulomas and mycetomas, and vascular rearrangement. We identified an unusual spatial arrangement of vasculature within an entire COVID-19 lobe, and 3D segmentation of …

The Divine Consumptive: The Depiction Of Tuberculosis In Jane Eyre, Haley Highfield

Theses and Dissertations

Disease was a constant and unavoidable facet of life in British society during the Victorian Era. Despite the overwhelming prevalence of disease, the true cause of these illnesses remained mysterious until the turn of the century. With the origins of many of these diseases being either unknown or ascribed to mistaken sources, effective treatment was an impossibility. Tuberculosis is a prime example of this conundrum. Even with an estimated twenty-five percent of the British population dying from this particular disease during the nineteenth century, the actual provenance for infection was not discovered until 1882 with Robert Koch’s identification of the …

Generation Of Mycobacterium Smegmatis Model Systems For Testing Inhibitors Of The Mycobactin Siderophore Of Mycobacterium Tuberculosis, Gabrielle A. Germain

Dissertations, Theses, and Capstone Projects

Mycobacterium tuberculosis (Mtb) is the pathogenic bacterium causative of tuberculosis. According to the 2021 World Health Organization (WHO) Global Tuberculosis (TB) Report, there were approximately 5.8 million TB cases in 2020, and 1.3 million TB deaths among HIV negative people in that year. The rise of multi-drug resistant Mtb strains has increased the need for more potent microbials against this pathogen. Biosynthesis of iron scavenging molecules, known as siderophores (e.g., mycobactin and carboxymycobactin), has been identified as a potential drug target candidate since iron acquisition has been directly linked to the survival and virulence of Mtb. Salicyl-AMS (Sal-AMS) is …

Novel Automation Of An Enzyme-Linked Immunosorbent Spot Assay Testing Method: Comparable Diagnostic Performance Of The T-Spot.Tb Test Using Manual Density Gradient Cell Isolation Versus Automated Positive Selection With The T-Cell Select Kit, Shu-Hua Wang, Murgesean V. S. Rajaram, Andre Trollip, Qian Wu, Doris Ayala, Danyelle Garza, Marielena A. Benavidez, Kelsie Fox, Genesis P. Aguillón-Durán, Blanca I. Restrepo

School of Medicine Publications

The diagnosis of latent tuberculosis (TB) infection (LTBI) is critical to improve TB treatment and control, and the T-SPOT.TB test is a commercial enzyme-linked immunosorbent spot assay used for this purpose. The objective of the study was to increase automation and extend the time between blood collection and processing for the T-SPOT.TB test from 0 to 8 h to 0 to 54 h. The previous maximum time between blood collection and processing for the T-SPOT.TB test is 32 h using T-Cell Xtend. For this, we compared the T-SPOT.TB test using manual peripheral blood mononuclear cell …

Patient Preferences For Strategies To Improve Tuberculosis Diagnostic Services In Zambia, Andrew D Kerkhoff, Lophina Chilukutu, Sarah Nyangu, Mary Kagujje, Kondwelani Mateyo, Nsala Sanjase, Ingrid Eshun-Wilson, Elvin H Geng, Diane V Havlir, Monde Muyoyeta

2020-Current year OA Pubs

Importance: Delayed engagement in tuberculosis (TB) services is associated with ongoing transmission and poor clinical outcomes.

Objective: To assess whether patients with TB have differential preferences for strategies to improve the public health reach of TB diagnostic services.

Design, Setting, and Participants: A cross-sectional study was undertaken in which a discrete choice experiment (DCE) was administered between September 18, 2019, and January 17, 2020, to 401 adults (>18 years of age) with microbiologically confirmed TB in Lusaka, Zambia. The DCE had 7 attributes with 2 to 3 levels per attribute related to TB service enhancements. Latent class analysis was …

Lower Sars-Cov-2 Seroprevalence Among Cancer Patients In Sub-Saharan Africa, For Yue Tso, Salum J. Lidenge, John R. Ngowi, Phoebe B. Peña, Ashley A. Clegg, Owen Ngalamika, Chacha J. Mwita, Julius Mwaiselage, Charles Wood

School of Medicine Faculty Publications

Background: Despite the high COVID-19 morbidity and mortality rates across the world, the reported rates in sub-Saharan Africa (SSA), which has a higher burden of other infectious diseases and overwhelmed healthcare systems, remain relatively low. This study aims to better understand the potential factors that contribute to this phenomenon, especially among cancer patients who are considered as a high-risk group for developing severe COVID-19. Methods: Plasma samples collected during the COVID-19 pandemic from SARS-CoV-2 unvaccinated cancer and potential blood donor populations were analyzed for SARS-CoV-2 (spike and nucleocapsid proteins) antibodies by an immunofluorescence assay. The relationships between SARS-CoV-2 seroprevalences and …

Reach, Implementation, And Effectiveness Of A Tuberculosis Preventive Therapy Intervention In Rural South Africa, Brittney Van De Water, Isabel Fulcher, Karl Le Roux

Sigma Foundation for Nursing Research Grant Reports

In this study, we will assess the reach, implementation, and effectiveness of a nurse-led home based intervention designed to deliver tuberculosis (TB) preventive therapy.

Crispr Detection Of Circulating Cell-Free Mycobacterium Tuberculosis Dna In Adults And Children, Including Children With Hiv: A Molecular Diagnostics Study, Zhen Huang, Sylvia M Lacourse, Alexander W Kay, Joshua Stern, Jaclyn N Escudero, Brady M Youngquist, Wenshu Zheng, Debrah Vambe, Muyalo Dlamini, Godwin Mtetwa, Lisa M Cranmer, Irene Njuguna, Dalton C Wamalwa, Elizabeth Maleche-Obimbo, Donald G Catanzaro, Christopher J Lyon, Grace John-Stewart, Andrew Dinardo, Anna M Mandalakas, Bo Ning, Tony Y Hu

Faculty, Staff and Students Publications

BACKGROUND: Tuberculosis remains a leading cause of global mortality, especially for adults and children living with HIV (CLHIV) underdiagnosed by sputum-based assays. Non-sputum-based assays are needed to improve tuberculosis diagnosis and tuberculosis treatment monitoring. Our aim in this study was to determine whether ultrasensitive detection of Mycobacterium tuberculosis cell-free DNA (Mtb-cfDNA) in blood can diagnose tuberculosis and evaluate tuberculosis treatment responses.

METHODS: In this molecular diagnostics study we analysed archived serum from two patient populations evaluated for tuberculosis in Eswatini and Kenya to detect Mtb-cfDNA, analysing serum from all individuals who had both sufficient serum volumes and clear diagnostic results. …

Antibody-Mediated Lilrb2-Receptor Antagonism Induces Human Myeloid-Derived Suppressor Cells To Kill Mycobacterium Tuberculosis, Vipul K. Singh, Arshad Khan, Yitian Xu, Sunny Mai, Licheng Zhang, Abhishek Mishra, Blanca I. Restrepo, Ping-Ying Pan, Shu-Hsia Chen

School of Medicine Publications

Tuberculosis is a leading cause of death in mankind due to infectious agents, and Mycobacterium tuberculosis (Mtb) infects and survives in macrophages (MФs). Although MФs are a major niche, myeloid-derived suppressor cells (MDSCs) are an alternative site for pathogen persistence. Both MФs and MDSCs express varying levels of leukocyte immunoglobulin-like receptor B (LILRB), which regulate the myeloid cell suppressive function. Herein, we demonstrate that antagonism of LILRB2 by a monoclonal antibody (mab) induced a switch of human MDSCs towards an M1-macrophage phenotype, increasing the killing of intracellular Mtb. Mab-mediated antagonism of LILRB2 alone and its combination with a pharmacological blockade …

Human Macrophages Exhibit Gm-Csf Dependent Restriction Of Mycobacterium Tuberculosis Infection Via Regulating Their Self-Survival, Differentiation And Metabolism, Abhishek Mishra, Vipul K. Singh, Chinnaswamy Jagannath, Margaret Sunitha Selvaraj, Selvakumar Subbian, Blanca I. Restrepo, Marie-Claire Gauduin, Arshad Khan

School of Medicine Publications

GM-CSF is an important cytokine that regulates the proliferation of monocytes/macrophages and its various functions during health and disease. Although growing evidences support the notion that GM-CSF could play a major role in immunity against tuberculosis (TB) infection, the mechanism of GM-CSF mediated protective effect against TB remains largely unknown. Here in this study we examined the secreted levels of GM-CSF by human macrophages from different donors along with the GM-CSF dependent cellular processes that are critical for control of M. tuberculosis infection. While macrophage of different donors varied in their ability to produce GM-CSF, a significant correlation was observed …

Bacille Calmette-Guérin Vaccine Reprograms Human Neonatal Lipid Metabolism In Vivo And In Vitro, Joann Diray-Arce, Asimenia Angelidou, Kristoffer Jarlov Jensen, Maria Giulia Conti, Rachel S Kelly, Matthew Pettengill, Mark Liu, Simon D Van Haren, Scott D Mcculloch, Greg Michelloti, Olubukola Idoko, Tobias R Kollmann, Beate Kampmann, Hanno Steen, Al Ozonoff, Jessica Lasky-Su, Christine S Benn, Ofer Levy

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Vaccines have generally been developed with limited insight into their molecular impact. While systems vaccinology enables characterization of mechanisms of action, these tools have yet to be applied to infants, who are at high risk of infection and receive the most vaccines. Bacille Calmette-Guérin (BCG) protects infants against disseminated tuberculosis (TB) and TB-unrelated infections via incompletely understood mechanisms. We employ mass-spectrometry-based metabolomics of blood plasma to profile BCG-induced infant responses in Guinea-Bissau in vivo and the US in vitro. BCG-induced lysophosphatidylcholines (LPCs) correlate with both TLR-agonist- and purified protein derivative (PPD, mycobacterial antigen)-induced blood cytokine production in vitro, raising the …