Repopulating Kupffer cells originate directly from hematopoietic stem cells.

BACKGROUND: Kupffer cells (KCs) originate from yolk-sac progenitors before birth. Throughout adulthood, they self-maintain independently from the input of circulating monocytes (MOs) at a steady state and are replenished within 2 weeks after having been depleted, but the origin of repopulating KCs in adults remains unclear. The current paradigm dictates that repopulating KCs originate from preexisting KCs or monocytes, but there remains a lack of fate-mapping evidence. METHODS: We first traced the fate of preexisting KCs and that of monocytic cells with tissue-resident macrophage-specific and monocytic cell-specific fate-mapping mouse models, respectively. Secondly, we performed genetic lineage tracing to determine the type of progenitor cells involved in response to KC-depletion in mice. Finally, we traced the fate of hematopoietic stem cells (HSCs) in an HSC-specific fate-mapping mouse model, in the context of chronic liver inflammation induced by repeated carbon tetrachloride treatment. RESULTS: By using fate-mapping mouse models, we found no evidence that repopulating KCs originate from preexisting KCs or MOs and found that in response to KC-depletion, HSCs proliferated in the bone marrow, mobilized into the blood, adoptively transferred into the liver and differentiated into KCs. Then, in the chronic liver inflammation context, we confirmed that repopulating KCs originated directly from HSCs. CONCLUSION: Taken together, these findings provided in vivo fate-mapping evidence that repopulating KCs originate directly from HSCs, which presents a completely novel understanding of the cellular origin of repopulating KCs and shedding light on the divergent roles of KCs in liver homeostasis and diseases.

Analysis of Common Respiratory Infected Pathogens in 3100 Children after the Coronavirus Disease 2019 Pandemic.

OBJECTIVE: To investigate the epidemiological features in children after the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This study collected throat swabs and serum samples from hospitalized pediatric patients of Renmin Hospital of Wuhan University, Wuhan, Hubei province, China before and after the COVID-19 pandemic. Respiratory infected pathogens [adenovirus (ADV), influenza virus A/B (Flu A/B), parainfluenza virus 1/2/3 (PIV1/2/3), respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP), and Chlamydia pneumoniae (CP)] were detected. The pathogens, age, and gender were used to analyze the epidemiological features in children after the COVID-19 pandemic. RESULTS: The pathogen detection rate was significantly higher in females than in males (P<0.05), and the infection of PIV1 and MP was mainly manifested. After the COVID-19 pandemic, PIV1, PIV3, RSV, and MP had statistically different detection rates among the age groups (P<0.05), and was mainly detected in patients aged 0-6 years, 0-3 years, 0-3 years, and 1-6 years, respectively. When comparing before the COVID-19 pandemic, the total detection rate of common respiratory pathogens was lower (P<0.05). Except for the increase in the detection rate of PIV1 and CP, the infection rate of other pathogens had almost decreased. CONCLUSION: The prevention and control measures for the COVID-19 pandemic effectively changed the epidemiological features of common respiratory tract infectious diseases in pediatric children.