Medical Microbiology Commons^™

Ifn-Γ Attenuates Eosinophilic Inflammation But Is Not Essential For Protection Against Rsv-Enhanced Asthmatic Comorbidity In Adult Mice, Abenaya Muralidharan, Md Bashir Uddin, Christopher Bauer, Wenzhe Wu, Xiaoyong Bao, Keer Sun

Journal Articles: Pathology and Microbiology

The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine IFN-γ is essential for protection against RSV and RSV-associated comorbidities in adult mice. We found that, distinct from influenza virus, prior RSV infection does not induce significant IFN-γ production and susceptibility to secondary Streptococcus pneumoniae infection in adult wild-type (WT) mice. In ovalbumin (OVA)-induced asthmatic mice, RSV super-infection increases airway neutrophil recruitment and inflammatory lung damage …

Realistic And Critical Review Of The State Of Systemic Anti-Microbial Peptides, Guangshun Wang, Abraham F. Mechesso

Journal Articles: Pathology and Microbiology

Antimicrobial peptide research remains active not only because of the growing antibiotic resistance problem but also our desire to understand the role of innate immune peptides in host defense. While numerous peptides are currently under active development for topical use, this article highlights peptides with systemic efficacy. The scaffolds of these peptides range from linear to cyclic forms. The neutropenic mouse model is well established to illustrate antimicrobial efficacy from direct killing. The majority of tests, however, are conducted using normal mice so that both direct antimicrobial and immune regulatory effects can be characterized. These systemic examples underscore the possibility …

Insect Cell Expression And Purification Of Recombinant Sars-Cov-2 Spike Proteins That Demonstrate Ace2 Binding, Lucas R. Struble, Audrey L. Smith, William E. Lutz, Gabrielle Grubbs, Satish Sagar, Kenneth W. Bayles, Prakash Radhakrishnan, Surender Khurana, Dalia El-Gamal, Gloria E. O. Borgstahl

Journal Articles: Pathology and Microbiology

The COVID-19 pandemic caused by SARS-CoV-2 infection has led to socio-economic shutdowns and the loss of over 5 million lives worldwide. There is a need for the identification of therapeutic targets to treat COVID-19. SARS-CoV-2 spike is a target of interest for the development of therapeutic targets. We developed a robust SARS-CoV-2 S spike expression and purification protocol from insect cells and studied four recombinant SARS-CoV-2 spike protein constructs based on the original SARS-CoV-2 sequence using a baculovirus expression system: a spike protein receptor-binding domain that includes the SD1 domain (RBD) coupled to a fluorescent tag (S-RBD-eGFP), spike ectodomain coupled …

Type I Ifn Signaling Protects Mice From Lethal Sars-Cov-2 Neuroinvasion., Md Bashir Uddin, Yuejin Liang, Shengjun Shao, Sunil Palani, Michael Mckelvey, Scott C. Weaver, Keer Sun

Journal Articles: Pathology and Microbiology

Multiple organ damage is common in patients with severe COVID-19, even though the underlying pathogenic mechanisms remain unclear. Acute viral infection typically activates type I IFN (IFN-I) signaling. The antiviral role of IFN-I is well characterized in vitro. However, our understanding of how IFN-I regulates host immune response to SARS-CoV-2 infection in vivo is incomplete. Using a human ACE2-transgenic mouse model, we show in the present study that IFN-I receptor signaling is essential for protection against the acute lethality of SARS-CoV-2 in mice. Interestingly, although IFN-I signaling limits viral replication in the lung, the primary infection site, it is dispensable …

Clinical Laboratory Testing Practices In Diffuse Gliomas Prior To Publication Of 2021 World Health Organization Classification Of Central Nervous System Tumors, Shakti H. Ramkissoon, Helen Fernandes, Dolores H. Lopez-Terrada, Meera R. Hameed, Dimitri G. Trembath, Julia A. Bridge, Neal I. Lindeman, Rhona J. Souers, Patricia Vasalos, Daniel J Brat, Joel T. Moncur

Journal Articles: Pathology and Microbiology

CONTEXT.—: Integration of molecular data into glioma classification supports diagnostic, prognostic, and therapeutic decision-making; however, testing practices for these informative biomarkers in clinical laboratories remain unclear.

OBJECTIVE.—: To examine the prevalence of molecular testing for clinically relevant biomarkers in adult and pediatric gliomas through review of a College of American Pathologists proficiency testing survey prior to the release of the 2021 World Health Organization Classification of Central Nervous System Tumors.

DESIGN.—: College of American Pathologists proficiency testing 2020 survey results from 96 laboratories performing molecular testing for diffuse gliomas were used to determine the use of testing for molecular biomarkers …

Ifn-Γ Transforms The Transcriptomic Landscape And Triggers Myeloid Cell Hyperresponsiveness To Cause Lethal Lung Injury, Atul K. Verma, Michael Mckelvey, Md Bashir Uddin, Sunil Palani, Meng Niu, Christopher Bauer, Shengjun Shao, Keer Sun

Journal Articles: Pathology and Microbiology

Acute Respiratory Distress Syndrome (ARDS) is an inflammatory disease that is associated with high mortality but no specific treatment. Our understanding of initial events that trigger ARDS pathogenesis is limited. We have developed a mouse model of inflammatory lung injury by influenza and methicillin-resistant Staphylococcus aureus (MRSA) coinfection plus daily antibiotic therapy. Using this pneumonic ARDS model, here we show that IFN-γ receptor signaling drives inflammatory cytokine storm and lung tissue damage. By single-cell RNA sequencing (scRNA-seq) analysis, we demonstrate that IFN-γ signaling induces a transcriptional shift in airway immune cells, particularly by upregulating macrophage and monocyte expression of genes …

Catabolic Ornithine Carbamoyltransferase Activity Facilitates Growth Of Staphylococcus Aureus In Defined Medium Lacking Glucose And Arginine, Itidal Reslane, Cortney R. Halsey, Amanda Stastny, Barbara J. Cabrera, Jong-Sam Ahn, Dhananjay Shinde, Madeline R. Galac, Margaret F. Sladek, Fareha Razvi, Mckenzie K. Lehman, Kenneth W. Bayles, Vinai Chittezham Thomas, Luke D. Handke, Paul D. Fey

Journal Articles: Pathology and Microbiology

Previous studies have found that arginine biosynthesis in Staphylococcus aureus is repressed via carbon catabolite repression (CcpA), and proline is used as a precursor. Unexpectedly, however, robust growth of S. aureus is not observed in complete defined medium lacking both glucose and arginine (CDM-R). Mutants able to grow on agar-containing defined medium lacking arginine (CDM-R) were selected and found to contain mutations within ahrC, encoding the canonical arginine biosynthesis pathway repressor (AhrC), or single nucleotide polymorphisms (SNPs) upstream of the native arginine deiminase (ADI) operon arcA1B1D1C1. Reverse transcription-PCR (RT-PCR) studies found that mutations within ccpA or ahrC or …

Exploring Epigenetic Reprogramming During Central Nervous System Infection, Zachary Van Roy, Tammy Kielian

Journal Articles: Pathology and Microbiology

Epigenetics involves the study of various modes of adaptable transcriptional regulation, contributing to cell identity, characteristics, and function. During central nervous system (CNS) infection, epigenetic mechanisms can exert pronounced control over the maturation and antimicrobial properties of nearly every immune cell type. Epigenetics is a relatively new field, with the first mention of these marks proposed only a half-century ago and a substantial body of immunological epigenetic research emerging only in the last few decades. Here, we review the best-characterized epigenetic marks and their functions as well as illustrate how various immune cell populations responding to CNS infection utilize these …

The Staphylococcus Aureus Cida And Lrga Proteins Are Functional Holins Involved In The Transport Of By-Products Of Carbohydrate Metabolism, Jennifer L. Endres, Sujata S. Chaudhari, Xinyan Zhang, Janani Prahlad, Shu-Qi Wang, Lily A. Foley, Sorin Luca, Jeffrey L. Bose, Vinai C. Thomas, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

The Staphylococcus aureus cidABC and lrgAB operons encode members of a well-conserved family of proteins thought to be involved in programmed cell death (PCD). Based on the structural similarities that CidA and LrgA share with bacteriophage holins, we have hypothesized that these proteins function by forming pores within the cytoplasmic membrane. To test this, we utilized a "lysis cassette" system that demonstrated the abilities of the cidA and lrgA genes to support bacteriophage endolysin-induced cell lysis. Typical of holins, CidA- and LrgA-induced lysis was dependent on the coexpression of endolysin, consistent with the proposed holin-like functions of these proteins. In …

Datasets For The Reporting Of Primary Tumour In Bone: Recommendations From The International Collaboration On Cancer Reporting (Iccr), Judith V. M. G. Bovée, Fleur Webster, Fernanda Amary, Daniel Baumhoer, J. L. Hans Bloem, Julia A. Bridge, Justin M. M. Cates, Enrique De Alava, Angelo Paolo Dei Tos, Kevin B. Jones, Annabelle Mahar, G. Petur Nielsen, Alberto Righi, Andrew J. Wagner, Akihiko Yoshida, Christopher D. M. Fletcher

Journal Articles: Pathology and Microbiology

BACKGROUND AND OBJECTIVES: Bone tumours are relatively rare and, as a consequence, treatment in a centre with expertise is required. Current treatment guidelines also recommend review by a specialised pathologist. Here we report on international consensus-based datasets for the pathology reporting of biopsy and resection specimens of bone sarcomas. The datasets were produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations.

METHODS AND RESULTS: According to the ICCR's process for dataset development, an international expert panel consisting of pathologists, an oncologic orthopaedic surgeon, a medical oncologist, and …

Improved Database Filtering Technology Enables More Efficient Ab Initio Design Of Potent Peptides Against Ebola Viruses, Thomas Ripperda, Yangsheng Yu, Atul Verma, Elizabeth Klug, Michellie Thurman, St. Patrick Reid, Guangshun Wang

Journal Articles: Pathology and Microbiology

The rapid mutations of viruses such as SARS-CoV-2 require vaccine updates and the development of novel antiviral drugs. This article presents an improved database filtering technology for a more effective design of novel antiviral agents. Different from the previous approach, where the most probable parameters were obtained stepwise from the antimicrobial peptide database, we found it possible to accelerate the design process by deriving multiple parameters in a single step during the peptide amino acid analysis. The resulting peptide DFTavP1 displays the ability to inhibit Ebola virus. A deviation from the most probable peptide parameters reduces antiviral activity. The designed …

Biofilms: Formation, Research Models, Potential Targets, And Methods For Prevention And Treatment, Yajuan Su, Jaime T. Yrastorza, Mitchell Matis, Jenna Cusick, Siwei Zhao, Guangshun Wang, Jingwei Xie

Journal Articles: Pathology and Microbiology

Due to the continuous rise in biofilm-related infections, biofilms seriously threaten human health. The formation of biofilms makes conventional antibiotics ineffective and dampens immune clearance. Therefore, it is important to understand the mechanisms of biofilm formation and develop novel strategies to treat biofilms more effectively. This review article begins with an introduction to biofilm formation in various clinical scenarios and their corresponding therapy. Established biofilm models used in research are then summarized. The potential targets which may assist in the development of new strategies for combating biofilms are further discussed. The novel technologies developed recently for the prevention and treatment …

The Challenges Of Combatting Antimicrobial Resistance In The Philippines, Janine Patricia G. Robredo, Michelle Ann B. Eala, Joseph A. Paguio, Maria Sonia S. Salamat, Leo Anthony G. Celi

Ateneo School of Medicine and Public Health Publications

No abstract provided.

Factors Associated With Hpv16 Cervical Precancerous Stage : Microbiome/Virome And Hpv16 E1, Thanayod Sasivimolrattana

Chulalongkorn University Theses and Dissertations (Chula ETD)

The human papillomavirus type 16 (HPV16) and/or high-risk (Hr-) HPV are the main causes of cervical cancer. The viral factors, such as the E6 and E7 oncogenes, have been recognized as the major factors of carcinogenesis. However, it is currently unknown how other HPV genes, particularly E1, contribute to the development of cancer. Beside HPV, another element that may contribute to the development of cervical cancer is the microbiota in the cervix. Cervical bacteriome and mycobiome have been the focus of numerous investigations; less is known about cervical virome, particularly when HPV is present. No study has investigated the entire …

Predicting Cancer Immunotherapy Response From Gut Microbiomes Using Machine Learning Models, Hai Liang, Jay-Hyun Jo, Zhiwei Zhang, Margaret A Macgibeny, Jungmin Han, Diana M Proctor, Monica E Taylor, You Che, Paul Juneau, Andrea B Apolo, John A Mcculloch, Diwakar Davar, Hassane M Zarour, Amiran K Dzutsev, Isaac Brownell, Giorgio Trinchieri, James L Gulley, Heidi H Kong

Faculty, Staff and Student Publications

Cancer immunotherapy has significantly improved patient survival. Yet, half of patients do not respond to immunotherapy. Gut microbiomes have been linked to clinical responsiveness of melanoma patients on immunotherapies; however, different taxa have been associated with response status with implicated taxa inconsistent between studies. We used a tumor-agnostic approach to find common gut microbiome features of response among immunotherapy patients with different advanced stage cancers. A combined meta-analysis of 16S rRNA gene sequencing data from our mixed tumor cohort and three published immunotherapy gut microbiome datasets from different melanoma patient cohorts found certain gut bacterial taxa correlated with immunotherapy response …

Decoding The Mystery Of Antibiotic Persistence, Tahmina Hossain

Electronic Theses and Dissertations

This work combines microbiology, molecular biology, Next-Generation Sequencing and system biology approaches to explore the mechanism of antibiotic persistence: a multi-drug tolerant, non-dividing, and metabolically altered state present in a subpopulation of cells due to phenotypic diversity rather than genetic variation (i.e. mutations). Persister can survive lethal antibiotic state and resuscitate after the treatment period is over. They are considered as the major contributing factor behind recurring infections. They also have a high mutation rate, which increases the chances of bacteria gaining antibiotic resistance. The formation of this phenotypic variant (persister) threatens the therapeutic effectiveness of antibiotics and understanding how …

Functional Analysis Of Laminin Subunit Beta-3 (Lamb3) In Hpv16 Positive Cervical Cancer Cell Lines, Warattaya Wattanathavorn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Nearly 100% cervical cancer cases are infected with high-risk (HR) HPV types, in which HR-HPV16 is found in >50%. The mechanism of cervical cell transformation is related to the powerful activity of viral E6 and E7 oncoproteins. The aim of this study is to identify key genes and their associated pathways through comprehensive bioinformatics analysis as well as to explore the effects of a significant gene in cervical cancer carcinogenesis. In this study, the transcriptome sequencing (RNA-seq) of HPV16 positive cervical cancer cell lines (SiHa and CaSki) was compared to HPV negative cervical cancer cell lines (C33A) to identify significant …

Effects Of Gaba On Inflammation And Intestinal Barrier Disruption, Tyrel W. Long

EWU Masters Thesis Collection

Gut dysbiosis and intestinal barrier disruption have been linked to multiple sclerosis (MS). Our previous works show that experimental autoimmune encephalomyelitis (EAE) induction modifies the gut's microbiota composition, reducing frequencies of gamma-aminobutyric acid (GABA)-producing bacteria. GABA levels are reduced in the brains and circulation of MS patients. We engineered Lactococcus lactis with extra copies of gadB (glutamic acid decarboxylase) and gadC (glutamate/GABA antiporter) to increase GABA levels produced by the bacterium (GAD-L. lactis). EAE studies showed that the treatment with GAD-L. lactis and not with a L. lactis control expressing an empty plasmid (P-L. lactis) reduced the severity of the …

Microbial Contamination And Metabolite Exposure Assessment During Waste And Recyclable Material Collection, Fabiola Salambaga, Loïc Wingert, Isabelle Valois, Nancy Lacombe, François Gouin, Julien Trépanier, Maximilien Debia, Ewelina Soszczyńska, Magdalena Twarużek, Robert Kosicki, Marta Dias, Susana Viegas, Liliana Caetano, Carla Viegas, Geneviève Marchand

Études primaires

Waste workers are exposed to bioaerosols when handling, lifting and dumping garbage. Bioaerosol exposure has been linked to health problems such as asthma, airway irritant symptoms, infectious, gastrointestinal and skin diseases, and cancer. Our objective was to characterize the exposure of urban collectors and drivers to inhalable bioaerosols and to measured the cytotoxic effect of air samples in order to evaluate their health risk.

Personal and ambient air sampling were conducted during the summer of 2019. Workers from 12 waste trucks collecting recyclables, organic waste or compost were evaluated. Bacteria and fungi were cultured, molecular biology methods were used to …

Small Bowel Stomas Are Associated With Higher Risk Of Circulating Food-Specific-Igg Than Patients With Organic Gastrointestinal Conditions And Colostomies, Walker K. Carson, Joseph L. Baumert, Jennifer Clarke, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Objective The effects of food sensitivity can easily be masked by other digestive symptoms in ostomates and are unknown. We investigated food-specific-IgG presence in ostomates relative to participants affected by other digestive diseases.

Design Food-specific-IgG was evaluated for 198 participants with a panel of 109 foods. Immunocompetency status was also tested. Jejunostomates, ileostomates, and colostomates were compared with individuals with digestive tract diseases with inflammatory components (periodontitis, eosinophilic esophagitis, duodenitis, ulcerative colitis, Crohn’s disease, and appendicitis), as well as food malabsorption due to intolerance. A logistic regression model with covariates was used to estimate the effect of the experimental data …

Synthetic Flavonoid Derivatives With Antiviral Activity Against Dengue And Chikungunya Viruses, Van Cao

Chulalongkorn University Theses and Dissertations (Chula ETD)

Dengue infection is one significant global health issue, as climate change exacerbated the spread of mosquito vectors. The Chikungunya virus is also a re-emerging arbovirus infection, which is transmitted by some similar vectors. Currently, no commercial antiviral drug is available to treat them. Previous reports suggested that several flavonoid derivatives inhibited mosquito-borne flaviviruses even at submicromolar levels, and one of them is a halogenated flavone derivative, 8-bromobaicalein, was a potential dengue and Zika replication inhibitor targeting flaviviral polymerase and also 3CLpro of SARS-CoV-2. This study characterized that 8-bromobaicalein inhibited chikungunya virus replication with EC50 of 0.49 ± 0.11 µM in …

Effect Of Candida Glabrata Β-Glucans On Immunosuppressive Properties Of Dendritic Cells, Phawida Tummamunkong

Chulalongkorn University Theses and Dissertations (Chula ETD)

β-glucan is a polysaccharide and consists of the backbone of β-(1, 3)-glucan and/or β-(1, 6)-glucan structures. β-glucans are extracted from the cell wall of Candida sp, including Candida glabrata. Interestingly, the biological activity of Candida β-glucan has been represented as a stimulator in the mechanism of immune responses. Dendritic cells are powerful antigen-presenting cells that play a significant role in both innate and adaptive immunity. In the present study, we evaluated the effect of C. glabrata β-glucans on dendritic cell (DC) immunologic responses. Firstly, bone marrow-derived DCs (BMDCs) were induced with C. glabrata β-glucans in a dose-dependent manner. The expression …

Generation Of Tolerogenic Dendritic Cells From Fcgr2b Deficient Lupus-Prone Mice For The Model Of Sle Therapy, Phuriwat Khiewkamrop

Chulalongkorn University Theses and Dissertations (Chula ETD)

Tolerogenic dendritic cells (tolDCs) are DCs with an immunoregulatory function, which can induce regulatory T cells (Tregs) and suppress the immune response. Currently, tolDCs-based treatment has become a promising therapeutic approach for organ transplantation and autoimmune disease. FcgRIIB is an inhibitory receptor widely expressed in B cells, myeloid cells, and DCs. The ablation of FcgRIIB in the murine model shows a spontaneous development of a lupus-like disease and might affect other immune cell regulation. There was limited information on tolDC induction in FcgRIIB defective mice. Thus, in this study, we studied the generation of tolDCs from the bone marrow-derived dendritic …

The Inhibitory Effect Of Combined Human Cathelicidin With Antibiotics On Antibiotic-Resistant Cutibacterium Acnes, Rakwaree Sriharat

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cutibacterium acnes is one of the major factors involved in the pathogenesis of acne vulgaris which sometimes develops antibiotic resistance particularly clindamycin- and doxycycline-resistant C. acnes. In this study, human cathelicidin (LL-37) which is a type of human antimicrobial peptide against a wide range of microorganisms was used. We investigated the antimicrobial activity of LL-37 on C. acnes isolated from patients with acne at the King Chulalongkorn Hospital using broth microdilution. Moreover, the synergistic effects of LL-37 with clindamycin and doxycycline were investigated using checkerboard microdilution, and time-killing assays. The cytotoxicity of LL-37 was also evaluated by MTT assay. The …

Gut Microbiota From Sjögren Syndrome Patients Causes Decreased T Regulatory Cells In The Lymphoid Organs And Desiccation-Induced Corneal Barrier Disruption In Mice, Laura Schaefer, Claudia M Trujillo-Vargas, Firas S Midani, Stephen C Pflugfelder, Robert A Britton, Cintia S De Paiva

Faculty, Staff and Students Publications

Sjögren syndrome (SS) is an autoimmune inflammatory disorder characterized by secretory dysfunction in the eye and mouth; in the eye, this results in tear film instability, reduced tear production, and corneal barrier disruption. A growing number of studies show that homeostasis of the ocular surface is impacted by the intestinal microbiome, and several 16S sequencing studies have demonstrated dysbiosis of the intestinal microbiota in SS patients. In this study, we utilized metagenomic sequencing to perform a deeper analysis of the intestinal microbiome using stools collected from sex- and age-matched healthy (n = 20), dry eye (n = 4) …

Effects Of Different Serum Supplements On Piggybac Cd19 Chimeric Antigen Receptor T Cells, Mulita Sanyanusin

Chulalongkorn University Theses and Dissertations (Chula ETD)

Chimeric Antigen Receptor (CAR) T cell is a novel therapy for relapse and refractory hematologic malignancy. Characteristics of CAR T cells is associated with clinical efficacy and toxicity. Type of serum supplements used during cultivation affect the immunophenotype and function of viral-based CAR T cells. This study explores the effect of serum supplements on non-viral piggyBac transposon CAR T cell production. PiggyBac CD19 CAR T cells were expanded in cultured conditions containing either fetal bovine serum, human AB serum, human platelet lysate or xeno-free serum replacement. Then, the effect of different serum supplements on cell expansion, transfection efficiency, immunophenotypes and …

The Effect Of Histone Methylation In Trained Innate Immunity Of Cord Blood Monocytes In Newborn Infants Of Chronic Hbv-Infected Mothers, Pennapa Plypongsa

Chulalongkorn University Theses and Dissertations (Chula ETD)

Newborns contract Hepatitis B virus (HBV) through exposure in utero from mothers who are infected with HBV. In newborn infant from chronic HBV-infected mothers, the immune system displays innate immune cell maturation and enhances immune response upon restimulation with unrelated pathogens such as bacteria. This pattern is called “trained immunity” or “innate immune memory”. Trained immunity is regulated by epigenetic programming, especially histone modification. To date, there is not report on the epigenetics to regulate trained immunity in HBV. Therefore, this study investigated the cytokines levels and expression levels of histone modification enzyme genes in HBV-exposed cord blood monocytes. Moreover, …

Study Of Thermodynamic Binding Between Ader And Ades In Two-Component Antibiotic Sensor Of Antibiotic Resistant Strains Of Acinetobacter Baumannii, Konrawee Thananon

Chulalongkorn University Theses and Dissertations (Chula ETD)

The proteins AdeR (response regulator) and AdeS (histidine kinase sensor) play a crucial role in regulating the efflux pump, which is responsible for removing antibiotics from bacterial cells. This regulation occurs through a two-component regulatory system (TCS) involving autophosphorylation. Upon receiving external signals, AdeS undergoes autophosphorylation, leading to the activation of AdeR, which in turn initiates the expression of target genes related to the efflux pump. In this study, both enzymes from the reference strain of Acinetobacter baumannii (ATCC19606) and antibiotic resistant strains (H1074 and G560) were cloned and expressed in E. coli. The enzymes were purified using an immobilized …

Macrophage Depletion Enhances Gut Dysbiosis And Severity In Sepsis Mouse Model, Pratsanee Hiengrach

Chulalongkorn University Theses and Dissertations (Chula ETD)

Macrophage is vital players in the responsiveness of the innate immune system against injury or infection. Although macrophage depletion is well-known for some emerging therapies, such as osteoporosis, osteopenia, and decreasing tumor-associated macrophages in melanoma, dysfunction of macrophages leads to an inability of an appropriate immune response and implicated in various disease processes, especially intestinal macrophages that play a key role in the gut immune system and the regulation of gastrointestinal physiology. To obtain an understanding of the role of sepsis-associated macrophages, clodronate was used for the dysfunction of mouse macrophages with and without cecal ligation and puncture (CLP) sepsis. …

Epigenetic Regulation In Trained And Tolerized Macrophages, Salisa Benjaskulluecha

Chulalongkorn University Theses and Dissertations (Chula ETD)

Innate immune memory is the phenomenon that can either enhance (trained) or suppress (tolerized) immune response by innate immune cells during the second encounter of the stimuli such as pathogens. Previous studies reported that epigenetic regulations critically regulate both types of innate immune memory. However, a complete understanding of the underlying mechanisms is still lacking. In this study, we performed a screening of an epigenetics compound library to identify inhibitors that affect ß-glucan (BG)-trained or LPS-tolerized macrophages. Among 181 compounds tested, various inhibitors targeting Aurora kinase, histone methyltransferase PRMT and EZH2, histone demethylase LSD1 and JMJD2, histone deacetylase 6 and …