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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 -
Clinical Microbiology Reviews Dec 2023Strongyloidiasis is a World Health Organization neglected tropical disease usually caused by , a parasitic worm with a complex life cycle. Globally, 300-600 million... (Review)
Review
Strongyloidiasis is a World Health Organization neglected tropical disease usually caused by , a parasitic worm with a complex life cycle. Globally, 300-600 million people are infected through contact with fecally contaminated soil. An autoinfective component of the life cycle can lead to chronic infection that may be asymptomatic or cause long-term symptoms, including malnourishment in children. Low larval output can limit the sensitivity of detection in stool, with serology being effective but less sensitive in immunocompromise. Host immunosuppression can trigger catastrophic, fatal hyperinfection/dissemination, where large numbers of larvae pierce the bowel wall and disseminate throughout the organs. Stable disease is effectively treated by single-dose ivermectin, with disease in immunocompromised patients treated with multiple doses. Strategies for management include raising awareness, clarifying zoonotic potential, the development and use of effective diagnostic tests for epidemiological studies and individual diagnosis, and the implementation of treatment programs with research into therapeutic alternatives and medication safety.
Topics: Animals; Child; Humans; Strongyloidiasis; Ivermectin; Strongyloides stercoralis; Immunocompromised Host; Immunosuppression Therapy
PubMed: 37937980
DOI: 10.1128/cmr.00033-23 -
Nature Cell Biology May 2024Cancer metastasis is a biologically complex process that remains a major challenge in the oncology clinic, accounting for nearly all of the mortality associated with... (Review)
Review
Cancer metastasis is a biologically complex process that remains a major challenge in the oncology clinic, accounting for nearly all of the mortality associated with malignant neoplasms. To establish metastatic growths, carcinoma cells must disseminate from the primary tumour, survive in unfamiliar tissue microenvironments, re-activate programs of proliferation, and escape innate and adaptive immunosurveillance. The entire process is extremely inefficient and can occur over protracted timescales, yielding only a vanishingly small number of carcinoma cells that are able to complete all of the required steps. Here we review both the cancer-cell-intrinsic mechanisms and microenvironmental interactions that enable metastatic colonization. In particular, we highlight recent work on the behaviour of already-disseminated tumour cells, since meaningful progress in treating metastatic disease will clearly require a better understanding of the cells that spawn metastases, which generally have disseminated by the time of initial diagnosis.
Topics: Humans; Tumor Microenvironment; Neoplasm Metastasis; Animals; Neoplasms
PubMed: 38714854
DOI: 10.1038/s41556-024-01409-8 -
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