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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 -
Cell Reports Dec 2023The expression of pro-lymphangiogenic VEGF-C in primary tumors is associated with sentinel lymph node metastasis in most solid cancer types. However, the impact of...
The expression of pro-lymphangiogenic VEGF-C in primary tumors is associated with sentinel lymph node metastasis in most solid cancer types. However, the impact of VEGF-C on distant organ metastasis remains unclear. Perivascular tumor-associated macrophages (TAMs) play a crucial role in guiding hematogenous spread of cancer cells by establishing metastatic pathways within the tumor microenvironment. This process supports breast cancer cell intravasation and metastatic dissemination. We show here that VEGF-C-expressing TAMs reduce the dissemination of mammary cancer cells to the lungs while concurrently increasing lymph node metastasis. These TAMs express podoplanin and interact with normalized tumor blood vessels expressing VEGFR3. Moreover, clinical data suggest inverse association between VEGF-C-expressing TAMs and breast cancer malignancy. Thus, our study elucidates the paradoxical role of VEGF-C-expressing TAMs in redirecting cancer cells to preferentially disseminate to lymph nodes rather than to lungs, partially achieved by normalizing tumor blood vessels and promoting lymphangiogenesis.
Topics: Humans; Female; Lymphatic Metastasis; Breast Neoplasms; Tumor-Associated Macrophages; Vascular Endothelial Growth Factor C; Lymphangiogenesis; Tumor Microenvironment
PubMed: 38041815
DOI: 10.1016/j.celrep.2023.113507 -
Affective Science Dec 2023Studying facial expressions is a notoriously difficult endeavor. Recent advances in the field of affective computing have yielded impressive progress in automatically...
UNLABELLED
Studying facial expressions is a notoriously difficult endeavor. Recent advances in the field of affective computing have yielded impressive progress in automatically detecting facial expressions from pictures and videos. However, much of this work has yet to be widely disseminated in social science domains such as psychology. Current state-of-the-art models require considerable domain expertise that is not traditionally incorporated into social science training programs. Furthermore, there is a notable absence of user-friendly and open-source software that provides a comprehensive set of tools and functions that support facial expression research. In this paper, we introduce Py-Feat, an open-source Python toolbox that provides support for detecting, preprocessing, analyzing, and visualizing facial expression data. Py-Feat makes it easy for domain experts to disseminate and benchmark computer vision models and also for end users to quickly process, analyze, and visualize face expression data. We hope this platform will facilitate increased use of facial expression data in human behavior research.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s42761-023-00191-4.
PubMed: 38156250
DOI: 10.1007/s42761-023-00191-4