Single-Cell RNA Sequencing Reveals Unique Alterations in the Immune Panorama and Treg Subpopulations in Mice during the Late Stages of Echinococcus granulosus Infection

Wu, Jianwen; Xiao, Jing; Bai, Min; Shi, Chunwei; Xin, Yunzhuo; Wang, Zhao; Gao, Xiaoping; Yin, Mei; Zhao, Jiaqing

doi:10.1128/iai.00029-23

Cited by 14 publications

(12 citation statements)

References 85 publications

(92 reference statements)

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“…Extensive research indicates that helminths use small microRNAs to manipulate their host’s immune responses by ‘cross-kingdom’ gene regulation ( Chowdhury et al, 2023 ). Advances in single-cell sequencing have significantly clarified the influence of the impact of Echinococcus on the immune microenvironment of the host ( Yasen et al, 2021 ; Jiang T. et al, 2022 ; Jiang X. et al, 2022 ; Wu et al, 2023 ). The second aspect addresses the effects of host on the parasite, including adapting to host microenvironment and evading host immunity.…”

Section: Discussionmentioning

confidence: 99%

“…Parasite–host interaction could be divided into two equal important aspects. Whereas most studies have focused on the effects of parasite on the host ( Yasen et al, 2021 ; Jiang T. et al, 2022 ; Jiang X. et al, 2022 ; Wu et al, 2023 ), relatively few studies have been reported concerning the effects of host on the parasite ( Hemer et al, 2014 ; Cheng et al, 2017 ). The most important impact of host on the parasite is immune response and the oxidative stress it induces.…”

Section: Introductionmentioning

confidence: 99%

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ROS are required for the germinative cell proliferation and metacestode larval growth of Echinococcus multilocularis

Tian,

Cheng,

et al. 2024

Front. Microbiol.

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The potentially lethal zoonotic disease alveolar echinococcosis (AE) is caused by the metacestode larval stages of the tapeworm Echinococcus multilocularis. Metacestode growth and proliferation occurs within the inner organs of mammalian hosts, which is associated with complex molecular parasite–host interactions. The host has developed various ways to resist a parasitic infection, and the production of reactive oxygen species (ROS) is one of the most important strategies. Here, we found that scavenging of ROS reduced metacestode larval growth and germinative cell proliferation in in vivo models. Furthermore, using in vitro-cultured metacestode vesicles, we found that increased ROS levels enhanced metacestode growth and germinative cell proliferation, which was achieved by positively activating the ROS-EmERK-EmHIF1α axis. These results indicate that, beside its capacity to damage the parasite, ROS also play critical roles in metacestode growth and germinative cell proliferation. This study suggests that the effects of ROS on parasite may be bidirectional during AE infection, reflecting the parasite’s adaptation to the oxidative stress microenvironment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ROS are required for the germinative cell proliferation and metacestode larval growth of Echinococcus multilocularis

Tian,

Cheng,

et al. 2024

Front. Microbiol.

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“…After washing, the samples were blocked with 5% BSA and incubated at room temperature for 1 h with the secondary antibody. Samples were then incubated in the dark with 10 μg/mL DAPI (Servicebio Technology Co., Ltd., China) in PBS for 10 min at room temperature, washed three times with PBS and mounted with Vectashield mounting medium (Vector Labs) [23, 24]. Images were acquired on a Nikon A1 confocal microscope.…”

Section: Methodsmentioning

confidence: 99%

Neutralizing gut-derived lipopolysaccharide as a novel therapeutic strategy for severe leptospirosis

Xie,

Chen,

Zhang

et al. 2024

Preprint

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Leptospirosis is an emerging infectious disease caused by pathogenicLeptospiraspp. Humans and some mammals can develop severe forms of leptospirosis accompanied by a dysregulated inflammatory response, which often results in death. The gut microbiota has been increasingly recognized as a vital element in systemic health. However, the precise role of the gut microbiota in severe leptospirosis is still unknown. Here, we aimed to explore the function and potential mechanisms of the gut microbiota in a hamster model of severe leptospirosis. Our study showed that leptospires were able to multiply in the intestine, cause pathological injury, and induce intestinal and systemic inflammatory responses. 16S rRNA gene sequencing analysis revealed thatLeptospirainfection changed the composition of the gut microbiota of hamsters with an expansion of Proteobacteria. In addition, gut barrier permeability was increased after infection, as reflected by a decrease in the expression of tight junctions. Translocated Proteobacteria were found in the intestinal epithelium of moribund hamsters, as determined by fluorescence in situ hybridization, with elevated LPS levels in the serum. Moreover, gut microbiota depletion reduced the survival time, increased the leptospiral load, and promoted the expression of proinflammatory cytokines afterLeptospirainfection. Intriguingly, fecal filtration and serum from moribund hamsters both increased the transcription ofTNF-α,IL-1β,IL-10, andTLR4in macrophages compared with those from uninfected hamsters. These stimulating activities were inhibited by LPS neutralization using polymyxin B. Based on our findings, we identified an LPS neutralization therapy that significantly improved the survival rates in severe leptospirosis when used in combination with antibiotic therapy or polyclonal antibody therapy. In conclusion, our study not only uncovers the role of the gut microbiota in severe leptospirosis but also provides a therapeutic strategy for severe leptospirosis.

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“…The fast-developing field of single-cell technologies have brought mechanistic insights into the host–pathogen interactions that influence viral ( 34 ), bacterial ( 35 ), fungal ( 36 ), and parasitic infections ( 37 ). In this study, we performed single-cell RNA-Seq (scRNA-Seq) analysis with murine splenocytes infected with green fluorescent protein expressing Bb (GFP+ Bb ) and compared the cellular and molecular patterns between Bb infected (GFP-positive) and bystander (GFP-negative) splenocytes.…”

Section: Introductionmentioning

confidence: 99%

Cellular and transcriptome signatures unveiled by single-cell RNA-Seq following ex vivo infection of murine splenocytes with Borrelia burgdorferi

Kumaresan,

Ingle,

Kilgore

et al. 2023

Front. Immunol.

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IntroductionLyme disease, the most common tick-borne infectious disease in the US, is caused by a spirochetal pathogen Borrelia burgdorferi (Bb). Distinct host responses are observed in susceptible and resistant strains of inbred of mice following infection with Bb reflecting a subset of inflammatory responses observed in human Lyme disease. The advent of post-genomic methodologies and genomic data sets enables dissecting the host responses to advance therapeutic options for limiting the pathogen transmission and/or treatment of Lyme disease.MethodsIn this study, we used single-cell RNA-Seq analysis in conjunction with mouse genomics exploiting GFP-expressing Bb to sort GFP+ splenocytes and GFP− bystander cells to uncover novel molecular and cellular signatures that contribute to early stages of immune responses against Bb.ResultsThese data decoded the heterogeneity of splenic neutrophils, macrophages, NK cells, B cells, and T cells in C3H/HeN mice in response to Bb infection. Increased mRNA abundance of apoptosis-related genes was observed in neutrophils and macrophages clustered from GFP+ splenocytes. Moreover, complement-mediated phagocytosis-related genes such as C1q and Ficolin were elevated in an inflammatory macrophage subset, suggesting upregulation of these genes during the interaction of macrophages with Bb-infected neutrophils. In addition, the role of DUSP1 in regulating the expression of Casp3 and pro-inflammatory cytokines Cxcl1, Cxcl2, Il1b, and Ccl5 in Bb-infected neutrophils were identified.DiscussionThese findings serve as a growing catalog of cell phenotypes/biomarkers among murine splenocytes that can be exploited for limiting spirochetal burden to limit the transmission of the agent of Lyme disease to humans via reservoir hosts.

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Single-Cell RNA Sequencing Reveals Unique Alterations in the Immune Panorama and Treg Subpopulations in Mice during the Late Stages of Echinococcus granulosus Infection

Cited by 14 publications

References 85 publications

ROS are required for the germinative cell proliferation and metacestode larval growth of Echinococcus multilocularis

ROS are required for the germinative cell proliferation and metacestode larval growth of Echinococcus multilocularis

Neutralizing gut-derived lipopolysaccharide as a novel therapeutic strategy for severe leptospirosis

Cellular and transcriptome signatures unveiled by single-cell RNA-Seq following ex vivo infection of murine splenocytes with Borrelia burgdorferi

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