Immunology and Infectious Disease Commons^™

Discovery Of Novel, Orally Bioavailable, Antileishmanial Compounds Using Phenotypic Screening, Diana Ortiz, W. Armand Guiguemde, Jared T. Hammill, Angela K. Carrillo, Yizhe Chen, Michele Connelly, Kayla Stalheim, Carolyn Elya, Alex Johnson, Jaeki Min, Anang Shelat, David C. Smithson, Lei Yang, Fangyi Zhu, R. Kiplin Guy, Scott M. Landfear

Pharmaceutical Sciences Faculty Publications

Leishmaniasis is a parasitic infection that afflicts approximately 12 million people worldwide. There are several limitations to the approved drug therapies for leishmaniasis, including moderate to severe toxicity, growing drug resistance, and the need for extended dosing. Moreover, miltefosine is currently the only orally available drug therapy for this infection. We addressed the pressing need for new therapies by pursuing a two-step phenotypic screen to discover novel, potent, and orally bioavailable antileishmanials. First, we conducted a high-throughput screen (HTS) of roughly 600,000 small molecules for growth inhibition against the promastigote form of the parasite life cycle using the nucleic acid …

Immune Checkpoint Inhibitors In Neuroendocrine Tumors: A Single Institution Experience With Review Of Literature, Aman Chauhan, Millicent Horn, Gray Magee, Kurt Hodges, B. Mark Evers, Susanne Arnold, Lowell B. Anthony

Markey Cancer Center Faculty Publications

This unique case series and review of literature suggests that immune checkpoint inhibitors may have clinical activity in neuroendocrine tumors.

Objective: Summarize advances of immuno-oncology in neuroendocrine tumors with the help of a case series.

Design: Case series and review of literature.

Intervention or Exposure: The patients were treated with immune checkpoint inhibitors (pembrolizumab or nivolumab).

Main Outcome(s) and Measures(s): Life expectancy, quality of life, disease progression.

Results: Maximum durable response of 16 months in one of the patients so far. All patients showed improvement in quality of life before disease progression. Two out of four are still on therapy. …

Ticks, Ixodes Scapularis, Feed Repeatedly On White-Footed Mice Despite Strong Inflammatory Response: An Expanding Paradigm For Understanding Tick-Host Interactions, Jennifer M. Anderson, Ian N. Moore, Bianca M. Nagata, José M.C. Ribeiro, Jesus G. Valenzuela, Daniel E. Sonenshine

Biological Sciences Faculty Publications

Ticks transmit infectious agents including bacteria, viruses and protozoa. However, their transmission may be compromised by host resistance to repeated tick feeding. Increasing host resistance to repeated tick bites is well known in laboratory animals, including intense inflammation at the bite sites. However, it is not known whether this also occurs in wild rodents such as white-footed mice, Peromyscus leucopus, and other wildlife, or if it occurs at all. According to the "host immune incompetence" hypothesis, if these mice do not have a strong inflammatory response, they would not reject repeated tick bites by Ixodes scapularis. To test …

Lipophosphoglycan Polymorphisms Do Not Affect Leishmania Amazonensis Development In The Permissive Vectors Lutzomyia Migonei And Lutzomyia Longipalpis, Paula M. Nogueira, Agna C. Guimarães, Rafael R. Assis, Jovana Sadlova, Jitka Myskova, Katerina Pruzinova, Jana Hlavackova, Salvatore J. Turco, Ana C. Torrecilhas, Petr Volf, Rodrigo P. Soares

Molecular and Cellular Biochemistry Faculty Publications

Background: Lipophosphoglycan (LPG) is a dominant surface molecule of Leishmaniapromastigotes. Its species-specific polymorphisms are found mainly in the sugars that branch off the conserved Gal(β1,4)Man(α1)-PO₄ backbone of repeat units. Leishmania amazonensis is one of the most important species causing human cutaneous leishmaniasis in the New World. Here, we describe LPG intraspecific polymorphisms in two Le. amazonensis reference strains and their role during the development in three sand fly species.

Results: Strains isolated from Lutzomyia flaviscutellata (PH8) and from a human patient (Josefa) displayed structural polymorphism in the LPG repeat units, possessing side chains with 1 and 2 β-glucose …

Defining The Role Of Neuropilin-2 In Macrophages: Implications In Tumor Associated Macrophages In Pancreatic Cancer, Sohini Roy

Theses & Dissertations

Macrophages are extremely heterogeneous and highly plastic hematopoietic cells that reside in all tissues and act as a bridge between the innate and adaptive arms of the immune responses. Besides, they undertake a wide array of housekeeping functions like, clearance of cellular debris that arise due to regular turnover in tissues, iron homeostasis, immune surveillance as well as tissue repair processes post inflammation. They are also causally associated with several clinical conditions, including cancer where the infiltration of macrophages contribute to disease progression, metastasis and therapy resistance, and thereby poor clinical outcome.

Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins …

Prevention Of Childhood Obesity And Diabetes, Karen Carig

Master's Projects and Capstones

One of the public health concerns that have been on the rise is childhood obesity and diabetes. The National Health and Nutrition Examination Survey indicate that approximately one-third of children in the United States are overweight or obese with 17% meeting criteria for obesity (Pulgaron and Delamater, 2014). This crisis exists nationally and internationally which can effect children in the following ways: physically, socially, psychologically and mentally. Although, genetics also play a role in these diseases, environmental factors, lifestyle preferences and cultural environmental play have a major influence. My internship with the Food Education Project covers a better understanding to …

Effects Of Gm-Csf On Dendritic Cells And Regulatory T Cells In Parkinson’S Disease Patients And Models Of Parkinson’S Disease, Charles Schutt

Theses & Dissertations

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. Pathologically, loss of nigrostriatal neurons and dopamine released by these neurons are responsible for PD motor symptoms. During PD, activation of resident microglia and infiltrating lymphocytes leads to progressive neuroinflammation and reduction in the number and function of regulatory immune cells. Neuroinflammation contributes to progressive neurodegeneration and declining motor function. Reducing neuroinflammation is the target for novel PD therapeutics. Our goal is to increase the number and function of regulatory T cells (Tregs) in PD patients to decrease neuroinflammation and reduce PD symptoms. One potential therapy is granulocyte-macrophage colony stimulating …

The Pul37 Tegument Protein Guides Alphaherpesvirus Retrograde Axonal Transport To Promote Neuroinvasion, Alexsia L. Richards, Patricia J. Sollars, Jared D. Pitts, Austin M. Stults, Ekaterina E. Heldwein, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

A hallmark property of the neurotropic alpha-herpesvirinae is the dissemination of infection to sensory and autonomic ganglia of the peripheral nervous system following an initial exposure at mucosal surfaces. The peripheral ganglia serve as the latent virus reservoir and the source of recurrent infections such as cold sores (herpes simplex virus type I) and shingles (varicella zoster virus). However, the means by which these viruses routinely invade the nervous system is not fully understood. We report that an internal virion component, the pUL37 tegument protein, has a surface region that is an essential neuroinvasion effector. Mutation of this region rendered …

An Investigation Of The Levels Of Pro-Inflammation Cytokines In The Brain Of Autoimmune Lewis Rats, Han Yang

Theses & Dissertations

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damage, as well as disability. A reported symptom of RA includes tissue inflammation disease and cognitive dysfunction. This study aimed to compare the concentration of selected cytokines in the cerebral cortex, hippocampus, hypothalamus, amygdala, and cerebellum of Lewis rats. Age and sex-matched Lewis rats were separated into two groups: control and adjuvant-induced RA. Twenty-eight days after the adjuvant injection, groups were sacrificed and brains dissected using the stereotaxic atlas of Paximos and Watson as a guide. Pro-inflammatory cytokines IL-1β, IL-6, and IL-23, plus the anti-inflammatory …

Changing Antimalarial Drug Sensitivities In Uganda, Stephanie Alexis Rasmussen

Dissertations, Masters Theses, Capstones, and Culminating Projects

Dihydroartemisinin-piperaquine (DP) has demonstrated excellent efficacy for the treatment and prevention of malaria in Uganda. However, resistance to both components of this regimen has emerged in Southeast Asia. The efficacy of artemether-lumefantrine, the first-line regimen to treat malaria in Uganda, has also been excellent, but continued pressure may select for parasites with decreased sensitivity to lumefantrine. To gain insight into current drug sensitivity patterns, ex vivo sensitivities were assessed and genotypes previously associated with altered drug sensitivity were characterized for 58 isolates collected in Tororo, Uganda from subjects presenting in 2016 with malaria from the community or as part of …

Improving Hpv Vaccination Series Initiation Rates And Compliance Among Indigent Women In South Texas, Ages 19-26, Through Provider Recommendation And Additional Clinic Funding: A Quality Improvement Project, Lacey Cudd

Doctor of Nursing Practice

The purpose of this quality improvement project was to increase human papillomavirus vaccination series initiation rates among indigent women, ages 19-26, at a clinic in South Texas. The human papillomavirus is a sexually transmitted infection that has been associated with multiple types of cancers. Each year, approximately 6.2 million cases of the human papillomavirus infection are diagnosed; as many as 75% of all new infections occur among females 18-26 years of age. The human papillomavirus vaccination has a high efficacy in regards to cancer prevention, preventing as many as 76% of cancers with only one dose. The project included educating …

Gastrointestinal Parasites In Captive And Free-Ranging Cebus Albifrons In The Western Amazon, Ecuador, Sarah Martin-Solano, Gabriel A. Carrillo-Bilbao, William Ramirez, Maritza Celi-Erazo, Marie-Claude Huynen, Bruno Levecke, Washington Benitez-Ortiz, Bertrand Losson

All Faculty Scholarship for the College of the Sciences

Currently, there is a lack of surveys that report the occurrence of gastrointestinal parasites in the whiteheaded capuchin monkey (Cebus albifrons). We therefore assessed the presence and richness (= number of different parasite genera) of parasites in C. albifrons in wildlife refuges (n = 11) and in a free-ranging group near a human village (n = 15) in the Ecuadorian Amazon. In the 78 samples collected (median of 3 samples per animal), we identified a total of 6 genera of gastrointestinal parasites, representing protozoa, nematodes, acanthocephalans and cestodes. We observed a high prevalence (84%) across the 26 individuals, with the …

Type Ix Secretion System: Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru

Electronic Theses and Dissertations

Porphyromonas gingivalis and Tannerella forsythia are two of the primary pathogens that are associated in the etiology and progression of chronic periodontitis. In T. forsythia, KLIKK proteases are the recently identified group of proteolytic enzymes that are secreted through Type IX secretion system (T9SS). Among, these KLIKK proteases a synergistic relationship was observed between karilysin and mirolysin in invading the host complement system for the survival of the bacteria. Since, karilysin has been already characterized, in this study we propose to study about mirolysin through structural, biochemical and biological characterization. The obtained results from the experiments has shown the …

Fluorescence-Reported Allelic Exchange Mutagenesis Reveals A Role For Chlamydia Trachomatis Tmea In Invasion That Is Independent Of Host Ahnak, M. J. Mckuen, Konrad E. Mueller, Y. S. Bae, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Development of approaches to genetically manipulate Chlamydia is fostering important advances in understanding pathogenesis. Fluorescence-reported allelic exchange mutagenesis (FRAEM) now enables the complete deletion of specific genes in C. trachomatis L2. We have leveraged this technology to delete the coding sequences for a known type III effector. The evidence provided here indicates that CT694/CTL0063 is a virulence protein involved in chlamydial invasion. Based on our findings, we designate the gene product corresponding to ct694-ctl0063 translocated membrane-associated effector A (TmeA). Deletion of tmeA did not impact development of intracellular chlamydiae. However, the absence of TmeA manifested as a decrease in infectivity …

A License To Kill: Understanding Natural Killer Cell Licensing To Fight Cancer, Jolie Schafer

Dissertations and Theses (Open Access)

Natural killer (NK) cell education is an essential developmental process for NK cell effector function, that renders some NK cells “licensed” and others “unlicensed” (with heightened or lowered effector function potential, respectively) against tumor and targets lacking self-molecules. However, the underlying mechanisms responsible for the heightened effector responses of licensed cells remain unknown. Using NK cells derived from humans and expanded ex vivo we performed high-throughput protein expression analysis, and identified multiple proteins that are differentially regulated in licensed and unlicensed human NK cells before and after inhibition by killer-cell immunoglobulin-like receptors (KIRs) and activation by the NKp46 natural cytotoxicity …

Mechanism Of Candida Albicans Biofilm And Virulence Inhibition By A Bacterial Secreted Factor, Carrie Graham

Dissertations and Theses (Open Access)

The human microbiome is a diverse polymicrobial population comprised of both fungi and bacteria. Perturbations of the normal microbiome can have a profound impact on health, including the development of infections. Exploitation of these polymicrobial interactions has the potential to provide novel treatment and prevention strategies for infectious diseases. Enterococcus faecalis, a Gram-positive bacterium, and Candida albicans, a polymorphic fungus, occupy overlapping niches as ubiquitous constituents of the gastrointestinal and oral microbiome. Both species are also amongst the most important and problematic, opportunistic nosocomial pathogens and are often co-isolated during infection. Surprisingly, these two species antagonize each other’s …

Zika Virus Encoding Nonglycosylated Envelope Protein Is Attenuated And Defective In Neuroinvasion, Arun Saravanakumar Annamalai, Aryamav Pattnaik, Bikash R. Sahoo, Ezhumalai Muthukrishnan, Sathish Kumar Natarajan, David Steffen, Hiep Vu, Gustavo A. Delhon, Fernando Osorio, Thomas M. Petro, Shi-Hua Xiang, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

ABSTRACT Zika virus (ZIKV), a mosquito-transmitted flavivirus responsible for sporadic outbreaks of mild and febrile illness in Africa and Asia, reemerged in the last decade causing serious human diseases, including microcephaly, congenital malformations, and Guillain-Barré syndrome. Although genomic and phylogenetic analyses suggest that genetic evolution may have led to the enhanced virulence of ZIKV, experimental evidence supporting the role of specific genetic changes in virulence is currently lacking. One sequence motif, VNDT, containing an N-linked glycosylation site in the envelope (E) protein, is polymorphic; it is absent in many of the African isolates but present in all isolates from the …

Memory Potential, Molecular Characterization, And Translational Applications Of The Novel Theo/Tceo T Cell Phenotype, Todd Bartkowiak, Todd Bartkowiak

Dissertations and Theses (Open Access)

T cells comprise a substantial arm of the immune system and are exquisitely adapted to combat pathogens and tumors. The inflammatory environment largely dictates the nature of T cell response. A hallmark of T cell-mediated immunity is formation of immunological memory; the ability to respond more potently to re-encounter with pathogens. The immune system is also capable of recognizing tumors as foreign, much like viral or bacterial pathogens. Tumors have evolved, though, to generate an immunosuppressive environment to avoid destruction. The field of immunotherapy seeks to overcome immune suppression, in part by targeting T cell co-receptors on the cell surface …

Dynamic Assessment Of Nk Cell Interactions With Pediatric Tumor Cells To Predict Response To Immunotherapy, Arianexys Aquino Lopez

Dissertations and Theses (Open Access)

Due to Natural Killer (NK) cells’ capacity to target tumor cells without prior sensitization, adoptive NK cell therapy represents a promising immunotherapy approach for pediatric cancer patients. Our laboratory has developed an NK cell expansion protocol that generates large quantities of NK cells for therapeutic infusion. Given that NK cells are heterogeneous, with variable receptor expression and potential to target tumor cells, the purpose of my study was to determine whether subpopulations of NK cells with enhanced anti-tumor potential could be identified for increased potency of the NK cell infusion product. In addition, we previously showed that our expanded NK …

Membrane Bound Il21 Promotes Natural Killer Cell Expansion Through Mir 124-3p Mediated Regulation, Anitha Somanchi

Dissertations and Theses (Open Access)

Natural Killer (NK) cells are cells of the innate immune system that act as first line of defense against viral infections and participate in tumor immune surveillance. NK cells do not cause graft versus host disease (GvHD), or require prior antigen exposure to exert anti-tumor activity, hence are an attractive choice for immunotherapy applications. Owing to small numbers of NK cells in peripheral blood (1-32%, with a 6% median), ex vivo expansion of NK cells is critical for NK cell adoptive immunotherapy, various expansion platforms have been explored over the decades. We developed a robust platform for ex vivo expansion …

Zika Virus Encoding Nonglycosylated Envelope Protein Is Attenuated And Defective In Neuroinvasion, Arun S. Annamalai, Aryamav Pattnaik, Bikash R. Sahoo, Ezhumalai Muthukrishnan, Sathish Kumar Natarajan, David Steffen, Hiep Vu, Gustavo Delho, Fernando Osorio, Thomas M. Petro, Shi-Hua Xiang, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Zika virus (ZIKV), a mosquito-transmitted flavivirus responsible for sporadic outbreaks of mild and febrile illness in Africa and Asia, reemerged in the last decade causing serious human diseases, including microcephaly, congenital malformations, and Guillain-Barré syndrome. Although genomic and phylogenetic analyses suggest that genetic evolution may have led to the enhanced virulence of ZIKV, experimental evidence supporting the role of specific genetic changes in virulence is currently lacking. One sequence motif, VNDT, containing an N-linked glycosylation site in the envelope (E) protein, is polymorphic; it is absent in many of the African isolates but present in all isolates from the recent …

Emerging Infectious Disease And The Imperiled Relict Leopard Frog, Anthony Wayne Waddle

UNLV Theses, Dissertations, Professional Papers, and Capstones

The disease chytridiomycosis, caused by the aquatic fungal pathogen Batrachochytrium dendrobatidis (Bd), has emerged as a major contributing factor for worldwide amphibian declines. Although relatively recently described, the impacts from the disease this pathogen causes have been definitively tied to amphibian declines, including some that occurred decades ago. In some cases, declines of individual species occurred with little documentation and are thus poorly understood. The relict leopard frog (Rana onca = Lithobates onca) has experienced such a decline and by the latter part of the 20th century only occurred in two general areas in southern Nevada. Recent research has found …

A Molecular Diagnostic Survey Of Pathogens And Parasites Of Honey Bees, Apis Mellifera L., From Arkansas And Oklahoma, Dylan Cleary

Graduate Theses and Dissertations

The health and viability of colonies of the honey bee, Apis mellifera, in the United States have fluctuated dramatically over the past decade. This poses a substantial threat to agricultural production in this country. Currently, no single factor has been identified for this decline. Rather, it has been suggested that the interaction between multiple biotic and abiotic stressors may be responsible. Among these factors are pesticides, habitat loss, climate and weather, parasites and pathogens, and colony management techniques. For this reason, it is important to examine the prevalence of honey bee parasite and pathogen infection at the state level in …

Morphological And Molecular Divergence Of Rhipicephalus Turanicus Tick From Albania And China, Hong-Yu Li, Shan-Shan Zhao, Sándor Hornok, Róbert Farkas, Li-Ping Guo, Chuang-Fu Chen, Ren-Fu Shao, Ji-Zhou Lv, Yuan-Zhi Wang

Harold W. Manter Laboratory of Parasitology: Library Materials

Rhipicephalus turanicus is an important tick species potentially carrying tickborne pathogens. Several tick species have obvious subspecies divergence. However few studies aimed to examine the existence of divergence within R. turanicus. Therefore, a detailed morphological and molecular analysis was conducted for comparing R. turanicus from the Mediterranean Basin (represented by Albania) and Central Asia (Northwestern China). Altogether 315 adult ticks of R. turanicus (103 from Albania and 212 from China) were morphologically and molecularly analysed. DNA samples were used for mitochondrial 16S rRNA and cox1 gene sequences analysis. In addition, as potentially genetic markers, three fragments including partial nad1-16S …

Age-Structured And Vaccination Models Of Devil Facial Tumor Disease, Christopher D. Bruno, Timothy Comar, Megan O. Powell, Adjo Tameklo

Spora: A Journal of Biomathematics

Tasmanian devil populations have been devastated by devil facial tumor disease (DFTD) since its first appearance in 1996. The average lifespan of a devil has decreased from six years to three years. We present an age-structured model to represent how the disease has affected the age and breeding structures of the population. We show that with the recent increase in the breeding of juvenile devils, the overall devil population will increase but not nearly to pre-DFTD levels. The basic reproductive number may be increased with the influx of young breeding devils. In addition, our model shows that the release of …

Cost-Effectiveness Analysis Of Targeted Herpes Zoster Vaccination In Adults 50-59 At Increased Cardiovascular Risk, Kathleen M. Glassner

USF Tampa Graduate Theses and Dissertations

Background: Over the last twenty years the incidence of herpes zoster (HZ) infection, also known as shingles, has been increasing among adults for unknown reasons. The economic burden of HZ is currently estimated at over $1 billion per year in the United States (U.S.) and is expected to increase as the susceptible adult population ages. HZ is caused by a re-activation of the varicella zoster virus (VZV), chicken pox, and more than 95% of adults living today carry the virus with a lifetime risk of 1 in 3 for developing HZ. In 2006 the FDA approved a vaccine for the …

Evaluation Of A Microsphere-Based Immunoassay (Mia) In Measuring Diagnostic And Prognostic Markers Of Dengue Virus Infection, Jason H. Ambrose

USF Tampa Graduate Theses and Dissertations

Infections with dengue viruses (DENV) constitute both a global problem as well as locally in Florida. DENV comprise four distinct serotypes of single-stranded RNA viruses and belong to the family Flaviviridae. DENV are among the most medically important arboviruses in the world and cases may currently exceed 400 million per annum. Additionally, dengue established its first recorded endemic transmission cycle in the state of Florida in over a half century, first within the Florida Keys during 2009-10 followed by an unrelated outbreak in Martin County in 2013. The clinical profile of DENV infections ranges from a mild febrile illness …

Emergence Of The L Phenotype In Group B Streptococci In The South Of Ireland, Katherine Hayes, Lesley Cotter, L. Barry, Fiona O'Halloran

Department of Biological Sciences Publications

Group B Streptococcal isolates (n = 235) from the South of Ireland were characterised by serotyping, antimicrobial susceptibility and determination of the phenotypic and genotypic mechanisms of resistance. Resistance to erythromycin and clindamycin was observed in 21·3% and 20·4% of the total population, respectively. The c-MLSB phenotype was the most common phenotype detected (62%), with ermB being the predominant genetic determinant, present in 84% of resistant isolates. The rare L phenotype was observed in 2·9% (n = 7) of isolates, four of which harboured the lsaC gene responsible for clindamycin resistance. Serotypes Ia, III and II were the most common …

Mode And Rate Of Evolution Of Haemosporidian Mitochondrial Genomes: Timing The Radiation Of Avian Parasites, M. Andreína Pacheco, Nubia E. Matta, Gediminas Valkiūnas, Patricia G. Parker, Beatriz Mello, Craig E. Stanley Jr., Miguel Lentino, Maria Alexandra Garcia-Amado, Michael Cranfield, Sergei L. Kosakovsky Pond, Ananias A. Escalante

Harold W. Manter Laboratory of Parasitology: Library Materials

Haemosporidians are a diverse group of vector-borne parasitic protozoa that includes the agents of human malaria; however, most of the described species are found in birds and reptiles. Although our understanding of these parasites’ diversity has expanded by analyses of their mitochondrial genes, there is limited information on these genes’ evolutionary rates. Here, 114 mitochondrial genomes (mtDNA) were studied from species belonging to four genera: Leucocytozoon, Haemoproteus, Hepatocystis, and Plasmodium. Contrary to previous assertions, the mtDNA is phylogenetically informative. The inferred phylogeny showed that, like the genus Plasmodium, the Leucocytozoon and Haemoproteus genera are not monophyletic groups. Although …

Nlrp10 Enhances Cd4+ T-Cell-Mediated Ifnγ Response Via Regulation Of Dendritic Cell-Derived Il-12 Release, Maurizio Vacca, Julia Böhme, Lisa Zambetti, Hanif Javanmard Khameneh, Bhairav S. Paleja, Federica Laudisi, Adrian W. S. Ho, Kurt Neo, Keith Weng Kit Leong, Mardiana Marzuki, Bernett Lee, Michael Poidinger, Laura Santambrogio, Liana Tsenova, Francesca Zolezzi, Gennaro De Libero, Amit Singhal, Alessandra Mortellaro

Publications and Research

NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a Nlrp10−/− mouse to delineate the role of NLRP10 in the host immune response and found that Nlrp10−/− dendritic cells (DCs) elicited sub-optimal IFNγ production by antigenspecific CD4+ T cells compared to wild-type (WT) DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, Nlrp10−/− DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident in vivo and affected IFNγ production by CD4+ T cells. Upon …