A5056299792- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Immune Cell Function and Interaction
- Insect symbiosis and bacterial influences
- Immune Response and Inflammation
- interferon and immune responses
- NF-κB Signaling Pathways
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Parasites and Host Interactions
- HIV Research and Treatment
- Reproductive System and Pregnancy
- Psoriasis: Treatment and Pathogenesis
- Asthma and respiratory diseases
- Urticaria and Related Conditions
- Endometriosis Research and Treatment
- Biochemical and Molecular Research
- CAR-T cell therapy research
- Pediatric health and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Mesenchymal stem cell research
- Natural product bioactivities and synthesis
- Multiple Myeloma Research and Treatments
- Vasculitis and related conditions
- Testicular diseases and treatments
National Institute of Allergy and Infectious Diseases
2013-2025
National Institutes of Health
2009-2025
Roche (Switzerland)
2025
Johns Hopkins University
2006-2011
Sidney Kimmel Comprehensive Cancer Center
2006-2011
Biologie Fonctionnelle Insectes et Interactions
2006
The University of Western Australia
2004
Commensal-specific T cells are flexible Barrier tissues, like the skin, sites where noninvasive commensal microbes constantly interact with resident cells. These encounters can result in commensal-specific cell responses that promote, for example, host defense and tissue repair. Harrison et al. show subsets of skin-resident interleukin-17A–producing CD4 + CD8 have a dual nature: They coexpress transcription factors direct antagonistic antimicrobial (type 17) antiparasite pro–tissue repair 2)...
Abstract IL-17 is the signature cytokine of recently discovered Th type 17 (Th17) cells, which are prominent in defense against extracellular bacteria and fungi as well autoimmune diseases, such rheumatoid arthritis experimental encephalomyelitis animal models. IL-25 a member family cytokines, but has been associated with Th2 responses instead may negatively cross-regulate Th17/IL-17 responses. can initiate an allergic asthma-like inflammation airways, includes recruitment eosinophils, mucus...
The origin and functional specialization of dermal macrophages in cutaneous infections have been little studied. In this paper, we show that a strain Leishmania major (L. Seidman [LmSd]) produces nonhealing lesions conventionally resistant C57BL/6 mice was more efficiently taken up by M2-polarized bone marrow (BM)–derived (BMDMs) vitro mannose receptor (MR)hi vivo compared with healing Friedlin V1). Both steady T helper type 1 (Th1) cell–driven inflammatory states, the MRhi showed M2...
Although the role of human IRF-5 in antiviral and inflammatory responses vitro has been well characterized, much remains to be elucidated about murine IRF-5. Murine IRF-5, unlike heavily spliced gene, is primarily expressed as a full-length transcript, with only single splice variant that was detected very low levels bone marrow C57BL/6J mice. This contains 288-nucleotide deletion from exons 4-6 exhibits impaired transcriptional activity. The can activated by both TBK1 MyD88 form homodimers...
Inflammatory monocytes can be manipulated by environmental cues to perform multiple functions. To define the role of during primary or secondary infection with an intra-phagosomal pathogen we employed Leishmania major-red fluorescent protein (RFP) parasites and multi-color flow cytometry enumerate infected uninfected inflammatory cells in skin. During infection, had altered maturation were initial mononuclear host cell for parasite replication. In contrast, at a distal site mice healed but...
For many arthropod vectors, the diverse bacteria and fungi that inhabit gut can negatively impact pathogen colonization. Our attempts to exploit antibiotic treatment of colonized Phlebotomus duboscqi sand flies in order improve their vector competency for Leishmania major resulted instead were refractory development transmissible infections due inability parasite survive colonize anterior midgut with infective, metacyclic stage promastigotes. The survival defect could be overcome by feeding...
Leishmania are protozoan parasites transmitted by the bite of sand fly vectors producing a wide spectrum diseases in their mammalian hosts. These diverse clinical outcomes directly associated with parasite strain and species diversity. Although reproduction is mainly clonal, cryptic sexual cycle capable hybrid genotypes has been inferred from population genetic studies demonstrated laboratory crosses. Experimentally, mating competence largely confined to promastigotes developing midgut. The...
The transcription factor Interferon Regulatory Factor 5 (IRF-5) has been shown to be involved in the induction of proinflammatory cytokines response viral infections and TLR activation play an essential role innate inflammatory response. In this study, we used experimental model visceral leishmaniasis investigate IRF-5 generation Th1 responses formation Th1-type liver granulomas Leishmania donovani infected mice. We show that TLR7-mediated is for development L. spleen during chronic...
Abstract Background Despite therapeutic advancements, the cellular and molecular heterogeneity of UC hinders effective treatment. We applied machine learning-based approaches to whole scanned images (WSI) H&E stained slides prepared from formalin-fixed, paraffin embedded intestinal mucosal biopsies etrolizumab clinical trials, aiming identify interactions signatures that define disease subtypes treatment responses. hypothesised cellular-basis non-response could be derived by linking...
We describe successful immunotherapy of murine AIDS (MAIDS) in C57BL/6J mice based on the elimination replicating CD4(+) regulator T cells. demonstrate that a single injection antimitotic drug vinblastine (Vb) given 14 days postinfection (p.i.) with LP-BM5 can prevent MAIDS progression. Treatment anti-CD4 mAb at p.i. is similarly able to MAIDS. other time points Vb or ineffective. The effect ablation dominantly suppressive cell population, as indicated by adoptive transfer and vivo depletion...
Leishmania donovani causes visceral leishmaniasis (VL), which is typically fatal without treatment. There substantial variation between individuals in rates of disease progression, response to treatment and incidence post-treatment sequelae, specifically post-kala-azar dermal (PKDL). Nevertheless, the majority infected people are asymptomatic carriers. Hamsters mice commonly used as models non-fatal VL, respectively. Host parasite genetics likely be important factors, but general reasons for...
Abstract Bcl-3 is an atypical member of the IκB family that has potential to positively or negatively modulate nuclear NF-κB activity in a context-dependent manner. Bcl-3’s biologic impact complex and includes roles tumorigenesis diverse immune responses, including innate immunity. may mediate LPS tolerance, suppressing cytokine production, but it also seems contribute defense against select systemic bacterial challenges. However, role organ-specific host bacteria not been addressed. In this...
Psoriasis is a relapsing skin disease characterized by abnormal keratinocyte proliferation and differentiation an influx of inflammatory immune cells. Recently, IL-17 cytokines have been strongly implicated as critical for the pathogenesis this disease. IL-17A (also known IL-17) IL-17F are signature Th17 cells, but also produced innate including γδ T cells present in skin, whereas epithelial keratinocytes, may produce IL-17C. signal via adaptor protein connection to IκB kinase...
Bcl-3 is an atypical member of the family IκB proteins. Unlike classic members, functions as a nuclear transcriptional cofactor that may, depending on context, promote or suppress genes via association with p50/NF-κB1 p52/NF-κB2 homodimers. also oncogene, because it partner in recurrent translocations B cell tumors, resulting deregulated expression. functions, however, remain poorly understood. We have investigated role cells and discovered previously unknown involvement splenic development...
Abstract Whole genome analysis of Leishmania hybrids generated experimentally in sand flies supports a meiotic mechanism genetic exchange, with Mendelian segregation the nuclear genome. Here, we perform functional analyses through generation double drug-resistant vitro and vivo (during fly infections) to assess importance conserved meiosis-related genes recombination plasmogamy. We report that HOP1 HAP2-paralog (HAP2-2) are essential components meiosis machinery cell-to-cell fusion...
Patients with active visceral leishmaniasis are important reservoirs in the anthroponotic transmission cycle of Leishmania donovani. The role blood or skin as a source infection to sand flies remains unclear, and possible effect multiple exposures fly bites on transmissibility has not been addressed.
In murine models of visceral leishmaniasis (VL), parasitization resident Kupffer cells (resKCs) is responsible for early growth
Neutrophils rapidly infiltrate sites of infection and possess several microbicidal strategies, such as neutrophil extracellular traps release phagocytosis. Enhanced infiltration is associated with higher susceptibility to Leishmania infection, but effector response contribution this phenotype uncertain. Here, we show that neutrophils from susceptible BALB/c mice (B/c) produce more NETs in major than those resistant C57BL/6 (B6), which are phagocytic. The absence elastase contributes...
Leishmania is an intracellular parasite with different species pathogenic to humans and causing the disease leishmaniasis. donovani causes visceral leishmaniasis (VL) that manifests as hepatosplenomegaly, fever, pancytopenia hypergammaglobulinemia. If left without treatment, VL can cause death, especially in immunocompromised people. Current treatments have often significant adverse effects, resistance has been reported some countries. Determining metabolites perturbed during lead us find...
Abstract There is a considerable body of work exploring the role NF-κB family transcription factors in maturation and functions later stage B cells; however, their earlier bone marrow stages development less well understood despite demonstration that activity present at all early B-cell development. To explore consequences early, cell–targeted constitutive activation both pathways on development, we generated mice have either or both. constitutively activated beginning pro-B cells. In marked...