A5091319390- Leprosy Research and Treatment
- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Psoriasis: Treatment and Pathogenesis
- Immune Cell Function and Interaction
- Infectious Diseases and Tuberculosis
- Immune cells in cancer
- Immune Response and Inflammation
- Acne and Rosacea Treatments and Effects
- interferon and immune responses
- T-cell and B-cell Immunology
- Peripheral Neuropathies and Disorders
- Vitamin D Research Studies
- Pharmacological Effects of Natural Compounds
- Dermatology and Skin Diseases
- Cytokine Signaling Pathways and Interactions
- Yersinia bacterium, plague, ectoparasites research
- Erythrocyte Function and Pathophysiology
- Autophagy in Disease and Therapy
- Immunotherapy and Immune Responses
- Sphingolipid Metabolism and Signaling
- Toxin Mechanisms and Immunotoxins
- Hematological disorders and diagnostics
- Ocular Diseases and Behçet’s Syndrome
- Single-cell and spatial transcriptomics
University of California, Los Angeles
2014-2025
University of Southern California
2020
Indiana University School of Medicine
2020
UCLA Health
2019
Fundação Oswaldo Cruz
2000-2012
Faculdades Oswaldo Cruz
2009
Control of tuberculosis worldwide depends on our understanding human immune mechanisms, which combat the infection. Acquired T cell responses are critical for host defense against microbial pathogens, yet mechanisms by they act in humans remain unclear. We report that cells, release interferon-γ (IFN-γ), induce autophagy, phagosomal maturation, production antimicrobial peptides such as cathelicidin, and activity Mycobacterium macrophages via a vitamin D-dependent pathway. IFN-γ induced...
Interfering with Interferons Infections Mycobacteria, including Mycobacterium leprae or M. tuberculosis , vary substantially in their clinical presentation. For instance, some cases of the infection is self-healing very few lesions. In contrast, people experience disseminated form, where skin lesions abound and bacteria are abundant. patients infected Teles et al. (p. 1448 published online 28 February) found that disease associates a type I interferon gene signature, whereas form II...
Acne affects 1 in 10 people globally, often resulting disfigurement. The disease involves excess production of lipids, particularly squalene, increased growth Cutibacterium acnes, and a host inflammatory response with foamy macrophages. By combining single-cell spatial RNA sequencing as well ultrahigh-resolution Seq-Scope analyses early acne lesions on back skin, we identified TREM2 macrophages expressing lipid metabolism proinflammatory gene programs proximity to hair follicle epithelium...
IL-32 links the microbicidal peptide pathway with resistance to disease progression in clinical tuberculosis.
Triggering antimicrobial mechanisms in macrophages infected with intracellular pathogens, such as mycobacteria, is critical to host defense against the infection. To uncover unique and shared networks induced by innate adaptive immune systems, gene expression profiles generated RNA sequencing (RNAseq) from human monocyte-derived (MDMs) activated TLR2/1 ligand (TLR2/1L) or IFN-γ were analyzed. Weighed correlation network analysis identified modules of genes strongly correlated TLR2/1L that...
The immune system depends on effector pathways to eliminate invading pathogens from the host in vivo. Macrophages (MΦ) of innate are armed with vitamin D-dependent antimicrobial responses kill intracellular microbes. However, how physiological levels D during MΦ differentiation affect phenotype and function is unknown.The human consists divergent subsets that serve distinct functions Both IL-15 IL-10 induce differentiation, but induces primary monocytes differentiate into (IL-15 MΦ) robustly...
IL-26 is an antimicrobial protein secreted by Th17 cells that has the ability to directly kill extracellular bacteria. To ascertain whether contributes host defense against intracellular bacteria, we studied leprosy, caused obligate pathogen Mycobacterium leprae, as a model. Analysis of leprosy skin lesions gene expression profiling and immunohistology revealed was more strongly expressed in from self-limited tuberculoid compared with progressive lepromatous patients. bound M. leprae axenic...
TH17 cell subpopulations have been defined that contribute to inflammation and homeostasis, yet the characteristics of cells host defense against infection are not clear. To elucidate antimicrobial machinery subset, we studied response Cutibacterium acnes, a skin commensal is resistant IL-26, only known TH17-secreted protein with direct activity. We generated C. acnes–specific clones (AMTH17) varying activity which correlated by RNA sequencing expression transcripts encoding proteins...
Galectin-3 is a β-galactoside–binding lectin widely expressed on epithelial and hematopoietic cells, its expression frequently associated with poor prognosis in cancer. Because it has not been well-studied human infectious disease, we examined galectin-3 mycobacterial infection by studying leprosy, an intracellular caused Mycobacterium leprae. was highly macrophages lesions of patients the clinically progressive lepromatous form leprosy; contrast, almost undetectable self-limited tuberculoid...
Abstract Sequencing-based spatial transcriptomics (sST) enables transcriptome-wide gene expression mapping but falls short of reaching the optical resolution (200–300 nm) imaging-based methods. Here, we present Seq-Scope-X (Seq-Scope-eXpanded), which empowers submicrometer-resolution Seq-Scope with tissue expansion to surpass this limitation. By physically enlarging tissues, minimizes transcript diffusion effects and increases feature density by an additional order magnitude. In liver...
Abstract Macrophages orchestrate immune responses by sensing and responding to pathogen-associated molecules. These are modulated prior conditioning with cytokines such as interferons (IFNs). Type I II IFN have opposing functions in many biological scenarios, yet macrophages directly stimulated or activate highly overlapping gene expression programs. We hypothesized that a sequential conditioning-stimulation approach would reveal greater specificity the differential effects of on human...
Abstract Early diagnosis of leprosy is challenging, particularly its inflammatory reactions, the major cause irreversible neuropathy in leprosy. Current diagnostics cannot identify which patients are at risk developing reactions. This study assessed blood RNA expression levels as potential biomarkers for Prospective cohorts newly diagnosed patients, including and healthy controls were recruited Bangladesh, Brazil, Ethiopia Nepal. 1,090 whole samples was determined 103 target genes innate...
Transcriptome profiles derived from the site of human disease have led to identification genes that contribute pathogenesis, yet complex mixture cell types in these lesions has been an obstacle for defining specific mechanisms. Leprosy provides outstanding model study host defense and pathogenesis a infectious disease, given its clinical spectrum, which interrelates with immunologic pathologic responses. Here, we investigated gene expression skin each subtype leprosy, analyzing coexpression...
As circulating monocytes enter the site of disease, local microenvironment instructs their differentiation into tissue macrophages (MΦ). To identify mechanisms that regulate MΦ differentiation, we studied human leprosy as a model, since M1-type antimicrobial predominate in lesions self-limited form, whereas M2-type phagocytic are characteristic progressive form. Using heterotypic co-culture found unstimulated endothelial cells (EC) trigger to become M2 MΦ. However, biochemical screens...
Reversal reactions (RRs) in leprosy are characterized by a reduction the number of bacilli lesions associated with an increase cell-mediated immunity against intracellular bacterium Mycobacterium leprae, causative pathogen leprosy. To identify mechanisms that contribute to leprosy, we measured changes whole blood-derived transcriptome patients before, during and after RR. We identified 'RR signature' 1017 genes were upregulated at time clinical diagnosis Using weighted gene correlated...
The development of deformities during the course leprosy disease is a major public health concern worldwide. It possible that cytokine production and apoptosis Schwann cells (SCs) directly affect nerve degeneration regeneration leading to injury myelin sheath axon. In present study, expression TNFα, TGFβ, their receptors, in addition cell death triggered by cytokines or whole Mycobacterium leprae were investigated human SC line. results showed presence TNF-Rs TGF-RII on membrane shedding...
Abstract Matrix metalloproteinases (MMPs) and tumor necrosis factor alpha (TNF‐α) play important related roles in the pathogenesis of nerve injury. MMP‐dependent TNF‐α‐dependent processes neurodegeneration, such as blood‐nerve breakdown immune cell recruitment, are characteristic leprosy damage. Our work has contributed to understanding role cytokines process, but MMPs neuritic not been investigated. This study analyzed changes mRNA expression immunodistribution MMP‐2, MMP‐9,...
Gelatinases A and B (matrix metalloproteinase 2 [MMP-2] MMP-9, respectively) can induce basal membrane breakdown leukocyte migration, but their role in leprosy skin inflammation remains unclear. In this study, we analyzed clinical specimens from patients taken stable, untreated lesions during reactional episodes (reversal reaction [RR] erythema nodosum leprosum [ENL]). The participation of MMPs disease was suggested by (i) increased MMP mRNA expression levels biopsy correlating with the...