A5022440739- Inflammasome and immune disorders
- Immune Response and Inflammation
- Heme Oxygenase-1 and Carbon Monoxide
- Immune Cell Function and Interaction
- interferon and immune responses
- IL-33, ST2, and ILC Pathways
- Kawasaki Disease and Coronary Complications
- Immunotherapy and Immune Responses
- Research on Leishmaniasis Studies
- Viral Infections and Vectors
- Streptococcal Infections and Treatments
- Vector-borne infectious diseases
- Cancer Immunotherapy and Biomarkers
- Complement system in diseases
- Urticaria and Related Conditions
- Cell death mechanisms and regulation
- Influenza Virus Research Studies
- Autoimmune and Inflammatory Disorders Research
- T-cell and B-cell Immunology
- Drug-Induced Hepatotoxicity and Protection
- Calcium signaling and nucleotide metabolism
- Pediatric health and respiratory diseases
- Asthma and respiratory diseases
- Toxoplasma gondii Research Studies
- Inflammation biomarkers and pathways
Cedars-Sinai Medical Center
2016-2024
Lung Institute
2018-2024
University of Iowa
2010-2019
Veterans Health Administration
2010-2017
Inflammation Research Foundation
2008-2016
Iowa City VA Medical Center
2013-2015
Institute of Immunology
2010-2014
Iowa Policy Project
2014
University of Iowa Hospitals and Clinics
2012
Yale University
2005-2010
Mammalian Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs). Although TLRs are clearly involved detection bacteria and viruses, relatively little is known about their function response to eukaryotic microorganisms. Here we identify a profilin-like molecule from protozoan parasite Toxoplasma gondii that generates potent interleukin-12 (IL-12) murine DCs dependent on myeloid differentiation factor 88. T. profilin activates through...
Inhalation of crystalline silica and asbestos is known to cause the progressive pulmonary fibrotic disorders silicosis asbestosis, respectively. Although alveolar macrophages are believed initiate these inflammatory responses, mechanism by which this occurs has been unclear. Here we show that response subsequent development fibrosis after inhalation dependent on Nalp3 inflammasome. Stimulation with results in activation caspase-1 a Nalp3-dependent manner. Macrophages deficient components...
Dying cells are capable of activating the innate immune system and inducing a sterile inflammatory response. Here, we show that necrotic sensed by Nlrp3 inflammasome resulting in subsequent release proinflammatory cytokine IL-1β. Necrotic produced pressure disruption, hypoxic injury, or complement-mediated damage were inflammasome. activation was triggered part through ATP mitochondria released from damaged cells. Neutrophilic influx into peritoneum response to vivo also markedly diminished...
Hepatocyte death results in a sterile inflammatory response that amplifies the initial insult and increases overall tissue injury. One important example of this type injury is acetaminophen-induced liver injury, which toxic followed by innate immune activation. Using mice deficient Tlr9 inflammasome components Nalp3 (NACHT, LRR, pyrin domain–containing protein 3), ASC (apoptosis-associated speck-like containing CARD), caspase-1, we have identified nonredundant role for We shown acetaminophen...
Pseudomonas aeruginosa is a Gram-negative bacterium that causes opportunistic infections in immunocompromised individuals. P. employs type III secretion system to inject effector molecules into the cytoplasm of host cell. This interaction with cell leads inflammatory responses eventually result death. We show infection macrophages results activation caspase-1 an IPAF-dependent, but flagellin-independent, manner. Macrophages deficient IPAF or were markedly resistant aeruginosa–induced death...
To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control Mycobacterium tuberculosis, we compared outcome M. tuberculosis infection MyD88, TRIF/MyD88, IL-1R1, and IL-1beta-deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1beta signaling determining phenotype. Unexpectedly, infected TRIF/MyD88-deficient mice, rather than being defective expression,...
Caspase-1 is activated by a variety of stimuli after the assembly “inflammasome,” an activating platform made up complex NOD-LRR family proteins. required for secretion proinflammatory cytokines, such as interleukin (IL)-1β and IL-18, involved in control many bacterial infections. Paradoxically, however, its absence has been reported to confer resistance oral infection Salmonella typhimurium. We show here that caspase-1 or components inflammasome does not result S. typhimurium, but rather,...
The intraerythrocytic parasite Plasmodium—the causative agent of malaria—produces an inorganic crystal called hemozoin (Hz) during the heme detoxification process, which is released into circulation erythrocyte lysis. Hz rapidly ingested by phagocytes and induces production several pro-inflammatory mediators such as interleukin-1β (IL-1β). However, mechanism regulating recognition IL-1β maturation has not been identified. Here, we show that production. Using knockout mice, showed Hz-induced...
The proinflammatory cytokine IL-1beta plays an important role in antifungal immunity; however, the mechanisms by which fungal pathogens trigger secretion are unclear. In this study we show that infection with Candida albicans is sensed Nlrp3 inflammasome, resulting subsequent release of IL-1beta. ability C. to switch from a unicellular yeast form into filamentous essential for activation as mutants incapable forming hyphae were defective their induce macrophage IL- 1beta secretion....
Abstract Obesity is associated with an increased risk of developing breast cancer and also worse clinical prognosis. The mechanistic link between obesity progression remains unclear, there has been no development specific treatments to improve the outcome obese patients. Here we show that obesity-associated NLRC4 inflammasome activation/ interleukin (IL)-1 signalling promotes progression. tumour microenvironment in context induces increase tumour-infiltrating myeloid cells activated turn...
Pyroptosis is an inflammasome-mediated programmed cell death pathway triggered in macrophages by a variety of stimuli, including intracellular bacterial pathogens. Activation pyroptosis leads to the secretion interleukin-1β (IL-1β) and pore-mediated lysis. Although not considered pathogen, Candida albicans able kill and, thereby, escape from macrophages. Here, we show that C. albicans-infected bone marrow-derived (BMDM) murine J774 undergo pyroptotic suppressed glycine pharmacologic...
Interleukin (IL)-12 is a monocyte- and macrophage-derived cytokine that plays crucial role in both the innate acquired immune response. In this study, we examined effects ligating specific macrophage receptors had on induction of IL-12 by lipopolysaccharide (LPS). We report ligation Fcγ, complement, or scavenger inhibited LPS. Both mRNA synthesis protein secretion were diminished to near-undetectable levels following receptor ligation. Suppression was since IL-10 tumor necrosis factor-α...