A5010487949- Malaria Research and Control
- Cystic Fibrosis Research Advances
- Immune Response and Inflammation
- Inhalation and Respiratory Drug Delivery
- Legionella and Acanthamoeba research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Cell Function and Interaction
- Complement system in diseases
- Bacterial biofilms and quorum sensing
- Heme Oxygenase-1 and Carbon Monoxide
- RNA Research and Splicing
- Inflammasome and immune disorders
- interferon and immune responses
- Immune cells in cancer
- Mosquito-borne diseases and control
- RNA and protein synthesis mechanisms
- Biosensors and Analytical Detection
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Cardiovascular and exercise physiology
- Parasites and Host Interactions
- Air Quality and Health Impacts
- Animal Behavior and Reproduction
- Immune responses and vaccinations
University of Washington
2018-2025
Agenzia Regionale per la Protezione Ambientale del Piemonte
2020
University of California, Berkeley
2007-2019
University of California, San Francisco
2013-2019
International Centre for Genetic Engineering and Biotechnology
2017-2018
Gonzaga University
2006-2007
IRCCS Istituto Auxologico Italiano
1992-2007
University of Pennsylvania
2005
University of North Carolina at Chapel Hill
2005
Wake Forest University
2005
Caspases are either apoptotic or inflammatory. Among inflammatory caspases, caspase-1 and -11 trigger pyroptosis, a form of programmed cell death. Whereas both can be detrimental in disease, only has an established protective role during infection. Here, we report that caspase-11 is required for innate immunity to cytosolic, but not vacuolar, bacteria. Although Salmonella typhimurium Legionella pneumophila normally reside the vacuole, specific mutants (sifA sdhA, respectively) aberrantly...
The innate immune system responds to unique molecular signatures that are widely conserved among microbes but not normally present in host cells. Compounds stimulate pathways may be valuable the design of novel adjuvants, vaccines, and other immunotherapeutics. cyclic dinucleotide cyclic-di–guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger plays critical regulatory roles many species bacteria produced by eukaryotic In vivo vitro studies have previously suggested...
The intracellular bacterial pathogen Legionella pneumophila causes an inflammatory pneumonia called Legionnaires' Disease. For virulence, L. requires a Dot/Icm type IV secretion system that translocates effectors to the host cytosol. lacking is recognized by Toll-like receptors (TLRs), leading canonical NF-κB-dependent transcriptional response. In addition, expressing functional potently induces unique targets, including proinflammatory genes such as Il23a and Csf2. Here we demonstrate this...
Exposure to Plasmodium falciparum is associated with circulating "atypical" memory B cells (atMBCs), which appear similar dysfunctional found in HIV-infected individuals. Functional analysis of atMBCs has been limited, one report suggesting these are not but produce protective antibodies. To better understand the function malaria-associated atMBCs, we performed global transcriptome cells, obtained from individuals living an area high malaria endemicity Uganda. Comparison gene expression data...
Abstract Legionella pneumophila is an intracellular bacterial pathogen that the cause of a severe pneumonia in humans called Legionnaires’ disease. A key feature L. pathogenesis rapid influx neutrophils into lungs, which occurs response to signaling via IL-1R. Two distinct cytokines, IL-1α and IL-1β, can stimulate type I IL-1β produced upon activation cytosolic sensors inflammasomes detect vitro vivo. Surprisingly, we find no essential role for neutrophil recruitment lungs pneumophila....
Abstract Activated macrophages are crucial for restriction of microbial infection but may also promote inflammatory pathology in a wide range both infectious and sterile conditions. The pathways that regulate macrophage activation therefore great interest. Recent studies silico have putatively identified key transcription factors control activation, experimental validation is lacking. In this study, we generated regulatory network from publicly available microarray data, employing steps to...
FCRL5+ atypical memory B cells (atMBCs) expand in many chronic human infections, including recurrent malaria, but studies have drawn opposing conclusions about their function. Here, mice infected with Plasmodium chabaudi, we demonstrate expansion of an antigen-specific population that is distinct from previously described innate-like murine subsets. Comparative analyses reveal overlapping phenotypic and transcriptomic signatures between Plasmodium-infected atMBCs Plasmodium-exposed humans....
Inflammasomes are cytosolic multi-protein complexes that detect infection or cellular damage and activate the Caspase-1 (CASP1) protease. The NAIP5/NLRC4 inflammasome detects bacterial flagellin is essential for resistance to flagellated intracellular bacterium Legionella pneumophila. effectors required downstream of restrict replication remain unclear. Upon activation, CASP1 cleaves activates pore-forming protein Gasdermin-D (GSDMD) effector caspase-7 (CASP7). However, Casp1–/– (and...
Macrophages from the C57BL/6 (B6) mouse strain restrict intracellular growth of Legionella pneumophila, whereas A/J macrophages are highly permissive. The mechanism by which B6 remains poorly understood, but is known to require cytosolic microbe sensors Naip5 (Birc1e) and Ipaf. We hypothesized that Ipaf may act in partnership with other antimicrobial signalling pathways macrophages. Indeed, we found lacking either tumour necrosis factor (TNF)-α or type I interferon (IFN) permissive for L....
Transcriptional reprogramming of macrophages upon Mycobacterium tuberculosis (Mtb) infection is widely studied; however, the significance alternate splicing (AS) in shaping cellular responses to mycobacterial infections not yet appreciated. Alternate can influence transcript stability or structure, function and localization corresponding proteins thereby altering protein stoichiometry physiological consequences. Using comprehensive analysis a time-series RNA-seq data obtained from human...
Work capacity and cardiopulmonary performance were studied in a group of 11 young obese subjects (BMI 39.9 kg/m2) 10 normal 22 kg/m2). First all they underwent an incremental cycle ergometer test up to exhaustion. Subsequently, every subject the two groups performed constant work rate at different loads estimate cardiac output (Q) below anaerobic threshold (AT) by 20-second CO2 rebreathing method. Obese had significantly lower AT (79 vs. 109 W). The ratio between oxygen uptake heart (VO2/HR)...
Innate immune recognition of malaria parasites is the critical first step in development host response. At present, Toll-like receptor 9 (TLR9) thought to play a central role sensing infection. However, we and others have observed that Tlr9(-/-) mice, contrast mice deficient downstream adaptor, Myeloid differentiation primary response gene 88 (MYD88), exhibit few deficiencies function during early infection with parasite Plasmodium chabaudi, implying another MYD88-dependent also contributes...
Two-signal models have a rich history in immunology. In the classic two-signal model of T-cell activation, signal one consists engagement receptor by antigen/major histocompatibility complex, whereas two arises from costimulatory ligands on antigen-presenting cells. A requirement for independent signals helps to ensure that responses are initiated only response bona fide infectious threats. Our studies led us conclude initiation innate immune pathogens also often requires signals: is...
ABSTRACT Studies of innate immunity in metazoans have largely focused on detection microbial molecules by host pattern recognition receptors (PRRs). A complementary mode immune recognition, based pathogen-encoded activities, has long been recognized plants, where it is termed effector-triggered immunity; however, little known about the possibility metazoans. Legionella pneumophila an intracellular bacterial pathogen that causes Legionnaires' disease, inflammatory pneumonia. We recently...
Multimeric immunoglobulin-like molecules arose early in vertebrate evolution, yet the unique contributions of multimeric IgM antibodies to infection control are not well understood. This is partially due difficulty distinguishing low-affinity IgM, secreted rapidly by plasmablasts, from high-affinity derived later-arising memory cells. We developed a pipeline express B cell receptors (BCRs) Plasmodium falciparum–specific IgM+ and IgG+ human cells (MBCs) as both IgG molecules. BCRs subsets...
β2AR desensitization in airway smooth muscle (ASM) mediated by inflammation has been proposed to contribute asthma pathogenesis and diminished efficacy of β-agonist therapy. Mechanistic insight into this phenomenon is largely conceptual lacks direct empirical evidence. Here, we employ molecular genetic strategies reveal mechanisms mediating cytokine effects on ASM responsiveness. Ectopic expression inhibitory peptide (PKI-GFP) or a mutant regulatory subunit PKA (RevAB-GFP) effectively...
Dynamic regulation of leukocyte population size and activation state is crucial for an effective immune response. In malaria, Plasmodium parasites elicit robust host expansion macrophages monocytes, but the underlying mechanisms remain unclear. Here we show that myeloid during P. chabaudi infection dependent upon both CD4+ T cells cytokine Macrophage Colony Stimulating Factor (MCSF). Single-cell RNA-Seq analysis on antigen-experienced revealed expression Csf1, gene encoding MCSF, in a...
Pseudomonas aeruginosa (PA) is an opportunistic, frequently multidrug-resistant pathogen that can cause severe infections in hospitalized patients. Antibodies against the PA virulence factor, PcrV, protect from death and disease a variety of animal models. However, clinical trials PcrV-binding antibody-based products have thus far failed to demonstrate benefit. Prior candidates were derivations antibodies identified using protein-immunized systems required extensive engineering optimize...
Malaria, caused by Plasmodium sp. parasites, is a leading cause of global morbidity and mortality. Cerebral malaria, characterized neurological symptoms, life-threatening complication malaria affecting over 500,000 young children in Africa every year. Because the prevalence severity cerebral better understanding underlying molecular mechanisms its pathology desirable could inform future development therapeutics. This study sought to clarify role Toll-like receptors (TLRs) promoting...
Summary Previously, we reported that infection of human macrophages with Mycobacterium tuberculosis ( Mtb ) results in massive alterations the pattern RNA splicing host. The finding gained significance since alternate spliced variants a same gene may have substantially different structure, function, stability, interaction partners, localization, and so forth, owing to inclusion or exclusion specific exons. To establish proof‐of‐concept; on how infection‐induced could impact protein...
In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). contrast, mice infected with develop sterilizing immunity, hindering progress in understanding mechanistic basis clinical immunity. Here we present a novel model which persistently P. chabaudi exhibit limited symptoms despite sustaining patent parasite burdens for many months. Characterization immune responses...
Naturally acquired immunity to malaria develops only after many years and repeated exposures, raising the question of whether Plasmodium parasites, etiological agents malaria, suppress ability dendritic cells (DCs) activate optimal T cell responses. We demonstrated recently that B cells, rather than DCs, are principal activators CD4 + in murine malaria. In present study, we further investigated factors might prevent DCs from priming -specific helper found were significantly less efficient at...
All amphibians are thought to possess two distinct types of dermal gland: mucous and granular. Mucous glands typically produce an acidic, flocculent carbohydrate positive secretion that keeps skin moist helps maintain homeostasis. In this study, we use a battery histochemical tests identify these traditional in the dermis plethodontid salamander Ensatina eschscholtzii. The periodic acid-Schiff, alcian blue, toluidine blue carmine reactions reveal absence both acidic glycosaminoglycans...