Tissue-resident macrophages (TRMΦ) are important immune sentinels responsible for maintaining tissue and immune homeostasis within their specific niche. Recently, the origins of TRMΦ have undergone ...intense scrutiny, in which now most TRMΦ are thought to originate early during embryonic development independent of hematopoietic stem cells (HSCs). We previously characterized two distinct subsets of mouse peritoneal cavity macrophages (MΦ) (large and small peritoneal MΦ) whose origins and relationship to both fetal and adult long-term (LT) HSCs have not been fully investigated. In this study, we employ highly purified LT-HSC transplantation and in vivo lineage tracing to show a dual ontogeny for large and small peritoneal MΦ, in which the initial wave of peritoneal MΦ is seeded from yolk sac-derived precursors, which later require LT-HSCs for regeneration. In contrast, transplanted fetal and adult LT-HSCs are not able to regenerate brain-resident microglia. Thus, we demonstrate that LT-HSCs retain the potential to develop into TRMΦ, but their requirement is tissue specific in the peritoneum and brain.
Abstract
The current paradigm posits that a single long-term hematopoietic stem cell (LT-HSC) is capable of regenerating all components of the immune system. However, recent studies have overturned ...this paradigm by showing that tissue-resident macrophages (in brain, skin, and liver) develop from fetal progenitors in the yolk sac that emerge separate from, and prior to, the LT-HSC.
Recently, we have identified novel subsets of tissue-resident macrophages in the mouse peritoneum, namely Small and Large Peritoneal Macrophages (SPM and LPM). Here, using Runx1 lineage-tracing assays, we show that, similar to brain microglia, both SPM and LPM emerge at around embryonic day 8 (E8), prior to, and independent of, the conventional LT-HSC. However, after E11, the fetal liver LT-HSC can be called upon to regenerate both SPM and LPM, but not microglia. Single-cell high-dimensional phenotypic and gene expression assays reveal that LT-HSC-derived SPM and LPM are phenotypically and functionally comparable to their E8-derived yolk sac counterpart. After birth, and throughout adulthood, both peritoneum and liver, but not the brain, call upon LT-HSCs in the bone marrow to continuously regenerate their fetal-derived tissue-resident macrophages.
These results suggest that the requirement for LT-HSCs to regenerate macrophages is tissue-specific. In rodents, both peritoneum and liver, but not the brain, might be exposed to injuries and other exogenous insults that could require constant regeneration of their tissue-resident macrophages. Collectively, these findings add a new layer to the complex developmental landscape of the myeloid lineage and challenge the current notion that tissue-resident macrophages develop independently of the LT-HSCs.
We generated and characterized a rhesus macaque induced pluripotent stem cell (iPSC) line using induced reprogramming of fibroblasts isolated from a rhesus macaque fetus. The fibroblasts were ...expanded and then reprogrammed using non-integrating Sendai virus technology. This line is available as riPSC05. The authenticity of riPSC05 was confirmed through the expression of pluripotent and self-renewal markers, in vitro-directed differentiation towards three germ layers (ectoderm, mesoderm, and endoderm), karyotyping, and STR analysis.
The B.1.1.529 (Omicron) variant, first detected in November 2021, was responsible for a surge in U.S. infections with SARS-CoV-2, the virus that causes COVID-19, during December 2021-January 2022 ...(1). To investigate the effectiveness of prevention strategies in household settings, CDC partnered with four U.S. jurisdictions to describe Omicron household transmission during November 2021-February 2022. Persons with sequence-confirmed Omicron infection and their household contacts were interviewed. Omicron transmission occurred in 124 (67.8%) of 183 households. Among 431 household contacts, 227 were classified as having a case of COVID-19 (attack rate AR = 52.7%).
The ARs among household contacts of index patients who had received a COVID-19 booster dose, of fully vaccinated index patients who completed their COVID-19 primary series within the previous 5 months, and of unvaccinated index patients were 42.7% (47 of 110), 43.6% (17 of 39), and 63.9% (69 of 108), respectively. The AR was lower among household contacts of index patients who isolated (41.2%, 99 of 240) compared with those of index patients who did not isolate (67.5%, 112 of 166) (p-value <0.01). Similarly, the AR was lower among household contacts of index patients who ever wore a mask at home during their potentially infectious period (39.5%, 88 of 223) compared with those of index patients who never wore a mask at home (68.9%, 124 of 180) (p-value <0.01). Multicomponent COVID-19 prevention strategies, including up-to-date vaccination, isolation of infected persons, and mask use at home, are critical to reducing Omicron transmission in household settings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Key Clinical Message
Baseline assessment and interval monitoring with a careful history, clinical examination, laboratory work‐up, and noninvasive imaging modalities may be beneficial for early ...detection of immune checkpoint inhibitor‐associated side effects.
Previous reports of immune checkpoint inhibitors' cardiotoxic effects include pericarditis, myocarditis, myocardial infarction, ventricular dysfunction, vasculitis, and electrical abnormalities. The authors report a case of acute heart failure caused by nivolumab‐induced cardiotoxicity in a middle‐aged man with advanced esophageal carcinoma with no previous cardiac history or significant cardiovascular risk factors.
This study examines mental health services in five different regions of the Dominican Republic (DR) from the perspectives of health care providers. The purpose of this research was to (1) examine ...existing mental health care services; (2) identify barriers to treatment and mental health services delivery; and (3) explore potential strategies to improve mental health services delivery. Thirty-seven health care workers including physicians, nurses, psychologists, governmental administrators, and non-governmental community health workers were part of five focus groups and subsequent follow-up interviews. Transcripts were coded and analysed to obtain the most parsimonious categories of themes. Results indicated that there is insufficient funding allocated to mental health. The unreliable distribution of psychiatric medications precludes care for patients with severe chronic mental illness. Stigmatising attitudes among health care providers influences the quality of care. The prevalence of domestic violence is a significant public health problem contributing to mental illness. In conclusion, our study findings call for a re-examination of priority public health foci, with special attention to mental health and domestic violence in the DR. From a policy perspective, mental health care should be integrated into primary care and coupled with provider and patient education to reduce stigma. A social determinants approach could ameliorate systemic factors contributing to mental illness.
We present a case of myocarditis in a 26-year-old pregnant woman at 29 weeks gestation. Despite optimal medical therapy, she experienced a cardiac arrest 10 days postadmission. An interdisciplinary ...team facilitated emergency delivery of her baby by perimortem (ie, during maternal cardiac arrest) Caesarean section and initiation of emergency mechanical circulatory support. A cardiac biopsy revealed a mixed eosinophilic and histiocytic infiltrate. After a course of steroid therapy, she experienced full recovery. Both the patient and the infant are alive and well. The case highlights the success of modern interdisciplinary care, as well as ongoing gaps in our knowledge of myocarditis.
We present a case of myocarditis in a 26-year-old pregnant woman at 29 weeks gestation. Despite optimal medical therapy, she experienced a cardiac arrest 10 days postadmission. An interdisciplinary ...team facilitated emergency delivery of her baby by perimortem (ie, during maternal cardiac arrest) Caesarean section and initiation of emergency mechanical circulatory support. A cardiac biopsy revealed a mixed eosinophilic and histiocytic infiltrate. After a course of steroid therapy, she experienced full recovery. Both the patient and the infant are alive and well. The case highlights the success of modern interdisciplinary care, as well as ongoing gaps in our knowledge of myocarditis. Résumé: Nous présentons un cas de myocardite chez une femme de 26 ans enceinte de 29 semaines, qui a subi un arrêt cardiaque 10 jours après son admission. Une équipe interdisciplinaire a favorisé l'accouchement d'urgence par césarienne perimortem (c.-à-d. durant l'arrêt cardiaque de la mère), et la mise en place en urgence d'une assistance mécanique. Une biopsie cardiaque a révélé un infiltrat mixte d’éosinophiles et d'histiocytes. Il y a eu récupération complète de la fonction ventriculaire après un traitement aux stéroïdes. La patiente et l'enfant sont en vie et se portent bien. Le cas témoigne de la réussite de la pratique moderne des soins interdisciplinaires, et met en lumière les lacunes actuelles de nos connaissances sur la myocardite.
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