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Immunity Aug 2023Invasive fungal infections are associated with high mortality rates, and the lack of efficient treatment options emphasizes an urgency to identify underlying disease...
Invasive fungal infections are associated with high mortality rates, and the lack of efficient treatment options emphasizes an urgency to identify underlying disease mechanisms. We report that disseminated Candida albicans infection is facilitated by interleukin-1 receptor antagonist (IL-1Ra) secreted from macrophages in two temporally and spatially distinct waves. Splenic CD169 macrophages release IL-1Ra into the bloodstream, impeding early neutrophil recruitment. IL-1Ra secreted by monocyte-derived tissue macrophages further impairs pathogen containment. Therapeutic IL-1Ra neutralization restored the functional competence of neutrophils, corrected maladapted hyper-inflammation, and eradicated the otherwise lethal infection. Conversely, augmentation of macrophage-secreted IL-1Ra by type I interferon severely aggravated disease mortality. Our study uncovers how a fundamental immunoregulatory mechanism mediates the high disease susceptibility to invasive candidiasis. Furthermore, interferon-stimulated IL-1Ra secretion may exacerbate fungal dissemination in human patients with secondary candidemia. Macrophage-secreted IL-1Ra should be considered as an additional biomarker and potential therapeutic target in severe systemic candidiasis.
Topics: Humans; Interleukin 1 Receptor Antagonist Protein; Candida albicans; Macrophages; Receptors, Interleukin-1; Sepsis
PubMed: 37478856
DOI: 10.1016/j.immuni.2023.06.023 -
Journal of Fungi (Basel, Switzerland) Oct 2023Valley fever or coccidioidomycosis is a pulmonary infection caused by species of fungi that are endemic to California and Arizona. Skeletal coccidioidomycosis accounts... (Review)
Review
Valley fever or coccidioidomycosis is a pulmonary infection caused by species of fungi that are endemic to California and Arizona. Skeletal coccidioidomycosis accounts for about half of disseminated infections, with the vertebral spine being the preferred site of dissemination. Most cases of skeletal coccidioidomycosis progress to bone destruction or spread to adjacent structures such as joints, tendons, and other soft tissues, causing significant pain and restricting mobility. Manifestations of such cases are usually nonspecific, making diagnosis very challenging, especially in non-endemic areas. The lack of basic knowledge and research data on the mechanisms defining susceptibility to extrapulmonary infection, especially when it involves bones and joints, prompted us to survey available clinical and animal data to establish specific research questions that remain to be investigated. In this review, we explore published literature reviews, case reports, and case series on the dissemination of coccidioidomycosis to bones and/or joints. We highlight key differential features with other conditions and opportunities for mechanistic and basic research studies that can help develop novel diagnostic, prognostic, and treatment strategies.
PubMed: 37888258
DOI: 10.3390/jof9101002 -
Virulence Dec 2023Infection with often triggers pathophysiologic perturbations that are further augmented by the inflammatory responses of the host, resulting in the severe clinical... (Review)
Review
Infection with often triggers pathophysiologic perturbations that are further augmented by the inflammatory responses of the host, resulting in the severe clinical conditions of Lyme disease. While our apprehension of the spatial and temporal integration of the virulence determinants during the enzootic cycle of is constantly being improved, there is still much to be discovered. Many of the novel virulence strategies discussed in this review are undetermined. Lyme disease spirochaetes must surmount numerous molecular and mechanical obstacles in order to establish a disseminated infection in a vertebrate host. These barriers include borrelial relocation from the midgut of the feeding tick to its body cavity and further to the salivary glands, deposition to the skin, haematogenous dissemination, extravasation from blood circulation system, evasion of the host immune responses, localization to protective niches, and establishment of local as well as distal infection in multiple tissues and organs. Here, the various well-defined but also possible novel strategies and virulence mechanisms used by to evade obstacles laid out by the tick vector and usually the mammalian host during colonization and infection are reviewed.
Topics: Animals; Humans; Borrelia burgdorferi; Virulence; Lyme Disease; Virulence Factors; Mammals
PubMed: 37814488
DOI: 10.1080/21505594.2023.2265015 -
Revista de La Facultad de Ciencias... Sep 2023When we recognize the importance of disseminating scientific knowledge, we recognize not only the potential it can have in the hands of the scientific community, but...
When we recognize the importance of disseminating scientific knowledge, we recognize not only the potential it can have in the hands of the scientific community, but also in the hands of society as a whole. From this premise, we first reflect, hoping that such reflection will lead us to commit ourselves to make dissemination actions accessible and non-discriminatory. "Equal access to science is not only a social and ethical requirement for human development, but also a necessity to fully exploit the potential of scientific communities around the world and to guide scientific progress in a way that meets the needs of humanity".
PubMed: 37773336
DOI: 10.31053/1853.0605.v80.n3.42305 -
BMB Reports Jun 2024Cancer cells metastasize to distant organs by altering their characteristics within the tumor microenvironment (TME) to effectively overcome challenges during the... (Review)
Review
Cancer cells metastasize to distant organs by altering their characteristics within the tumor microenvironment (TME) to effectively overcome challenges during the multistep tumorigenesis. Plasticity endows cancer cell with the capacity to shift between different morphological states to invade, disseminate, and seed metastasis. The epithelial-to-mesenchymal transition (EMT) is a theory derived from tissue biopsy, which explains the acquisition of EMT transcription factors (TFs) that convey mesenchymal features during cancer migration and invasion. On the other hand, adherent-to-suspension transition (AST) is an emerging theory derived from liquid biopsy, which describes the acquisition of hematopoietic features by AST-TFs that reprograms anchorage dependency during the dissemination of circulating tumor cells (CTCs). The induction and plasticity of EMT and AST dynamically reprogram cell-cell interaction and cell-matrix interaction during cancer dissemination and colonization. Here, we review the mechanisms governing cellular plasticity of AST and EMT during the metastatic cascade and discuss therapeutic challenges posed by these two morphological adaptations to provide insights for establishing new therapeutic interventions. [BMB Reports 2024; 57(6): 273-280].
Topics: Humans; Epithelial-Mesenchymal Transition; Cell Plasticity; Neoplasms; Tumor Microenvironment; Neoplastic Cells, Circulating; Neoplasm Metastasis; Transcription Factors; Animals; Neoplasm Invasiveness
PubMed: 38627950
DOI: No ID Found -
Matrix Biology : Journal of the... Apr 2024The largest mammalian organ, skin, consisting of a dermal connective tissue layer that underlies and supports the epidermis, acts as a protective barrier that excludes... (Review)
Review
The largest mammalian organ, skin, consisting of a dermal connective tissue layer that underlies and supports the epidermis, acts as a protective barrier that excludes external pathogens and disseminates sensory signals emanating from the local microenvironment. Dermal connective tissue is comprised of a collagen-rich extracellular matrix (ECM) that is produced by connective tissue fibroblasts resident within the dermis. When wounded, a tissue repair program is induced whereby fibroblasts, in response to alterations in the microenvironment, produce new ECM components, resulting in the formation of a scar. Failure to terminate the normal tissue repair program causes fibrotic conditions including: hypertrophic scars, keloids, and the systemic autoimmune connective tissue disease scleroderma (systemic sclerosis, SSc). Histological and single-cell RNA sequencing (scRNAseq) studies have revealed that fibroblasts are heterogeneous and highly plastic. Understanding how this diversity contributes to dermal homeostasis, wounding, fibrosis, and cancer may ultimately result in novel anti-fibrotic therapies and personalized medicine. This review summarizes studies supporting this concept.
Topics: Animals; Cicatrix, Hypertrophic; Epidermis; Fibroblasts; Fibrosis; Mammals; Scleroderma, Systemic; Skin
PubMed: 38423396
DOI: 10.1016/j.matbio.2024.02.009