Host-pathogen interactions are highly complex,involving large dynamic changes in gene expression during infection. These interactions are fundamental to understanding anti-infection immunity of hosts, as well as the p...Host-pathogen interactions are highly complex,involving large dynamic changes in gene expression during infection. These interactions are fundamental to understanding anti-infection immunity of hosts, as well as the pathogenesis of pathogens. For bacterial pathogens interacting with animal hosts, timeresolved dual RNA-seq of infected tissue is difficult to perform due to low pathogen load in infected tissue. In this study, an acute infection model of Larimichthys crocea infected by Pseudomonas plecoglossicida was established. The spleens of infected fish exhibited typical symptoms, with a maximum bacterial load at two days post-injection(dpi). Time-resolved dual RNA-seq of infected spleens was successfully applied to study hostpathogen interactions between L. crocea and P.plecoglossicida. The spleens of infected L. crocea were subjected to dual RNA-seq, and transcriptome data were compared with those of noninfected spleens or in vitro cultured bacteria. Results showed that pathogen-host interactions were highly dynamically regulated, with corresponding fluctuations in host and pathogen transcriptomes during infection. The expression levels of many immunogenes involved in cytokine-cytokine receptor,Toll-like receptor signaling, and other immunerelated pathways were significantly up-regulated during the infection period. Furthermore, metabolic processes and the use of oxygen in L. crocea were strongly affected by P. plecoglossicida infection. The WGCNA results showed that the metabolic process was strongly related to the entire immune process.For P. plecoglossicida, the expression levels of motility-related genes and flagellum assemblyrelated genes were significantly up-regulated. The results of this study may help to elucidate the interactions between L. crocea and P.plecoglossicida.展开更多
Active host-pathogen interactions take place during infection of human immunodeficiency virus type 1 (HIV-1). Outcomes of these interactions determine the efficiency of viral infection and subsequent disease progressi...Active host-pathogen interactions take place during infection of human immunodeficiency virus type 1 (HIV-1). Outcomes of these interactions determine the efficiency of viral infection and subsequent disease progression. HIV- infected cells respond to viral invasion with various defensive strategies such as innate, cellular and humoral immune antiviral mechanisms. On the other hand, the virus has also developed various offensive tactics to suppress these host cellular responses. Among many of the viral offensive strategies, HIV-1 viral auxiliary proteins (Tat, Rev, Nef, Vif, Vpr and Vpu) play important roles in the host-pathogen interaction and thus have significant impacts on the outcome of HIV infection. One of the best examples is the interaction of Vif with a host cytidine deaminase APOBEC3G. Although specific roles of other auxiliary proteins are not as well described as Vif-APOBEC3G interaction, it is the goal of this brief review to summarize some of the preliminary findings with the hope to stimulate further discussion and investiga- tion in this exhilarating area of research.展开更多
The prognosis of infectious diseases is determined by host-pathogen interactions.Control of pathogens has been the central dogma of treating infectious diseases in modern medicine,but the pathogen-directed medicine is...The prognosis of infectious diseases is determined by host-pathogen interactions.Control of pathogens has been the central dogma of treating infectious diseases in modern medicine,but the pathogen-directed medicine is facing significant challenges,including a lack of effective antimicrobials for newly emerging pathogens,pathogen drug resistance,and drug side effects.Here,a mathematic equation(ter-med equation of host-pathogen interactions,HPI-Equation)is developed to dissect the key variables of hostpathogen interactions.It shows that control of pathogens does not necessarily lead to host recov-ery.Instead,a combination of promoting a host’s power of self-healing and balancing immune responses provides the best benefit for host.Moreover,the HPI-Equation elucidates the scientific basis of traditional Chinese medicine(TCM),a host-based medicine that treats infectious diseases by promot-ing self-healing power and balancing immune responses.The importance of self-healing power eluci-dated in the HPIEquation is confirmed by recent studies that the tolerance mechanism,which is discovered in plants and animals and conceptually similar to self-healing power,improves host survival without directly attacking pathogens.In summary,the HPI-Equation describes host-pathogen interac-tions with mathematical logic and precision;it translates the ancient wisdoms of TCM into apprehen-sible modern sciences and opens a new venue for integrating TCM and modern medicine for a future medicine.展开更多
Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The pr...Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, Micro RNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.展开更多
Bacteria employ diverse immune systems,such as CRISPR-Cas,to fend offphage infections.A recent study un-covered the unprecedented mechanistic features of the Kongming bacterial defense system,which uniquely ex-ploits ...Bacteria employ diverse immune systems,such as CRISPR-Cas,to fend offphage infections.A recent study un-covered the unprecedented mechanistic features of the Kongming bacterial defense system,which uniquely ex-ploits phage-derived enzymes to synthesize deoxyinosine triphosphate(dITP),thereby triggering host immunity through NAD+depletion.In response,some phages have evolved countermeasures to disrupt dITP synthesis,highlighting the ongoing evolutionary arms race between hosts and pathogens.This discovery not only deepens our understanding of bacterial defense strategies but also paves the way for new insights in biomedical research and synthetic biology.展开更多
The red imported fire ant,Solenopsis invicta Buren,is a highly invasive eusocial insect pest that threatens native biodiversity,agriculture,and human health.The innate immune system and intricate social immune respons...The red imported fire ant,Solenopsis invicta Buren,is a highly invasive eusocial insect pest that threatens native biodiversity,agriculture,and human health.The innate immune system and intricate social immune responses of S.invicta pose challenges to the development of effective control strategies.Micro RNAs(mi RNAs)play critical roles in the post-transcriptional regulation of gene expression,which influences various biological processes,including immunity and host-pathogen interactions.While the mi RNA-mediated response of insects to pathogens has been extensively studied in solitary insects,little is known about the innate immune responses of individual members within a colony.To address this gap,we constructed small RNA libraries from Metarhizium anisopliae-infected S.invicta workers and investigated the temporal dynamics of mi RNA-mediated immune responses to the entomopathogen.Several differentially expressed mi RNAs were identified,and they were found to regulate genes involved in the Toll,IMD,and melanization immune pathways.Quantitative real-time PCR(q RT-PCR)was employed to analyze the spatiotemporal dynamics of key mi RNAs/target genes,specifically mi R-71/Mod SP1-Relish and mi R-7/Lysozyme2-Serine protease7.A dual luciferase assay(in vitro)was performed to validate the interactions between mi RNAs and their target genes.Overexpression of mi R-71 and mi R-7(via mi RNA mimics)efficiently suppressed their target genes,impaired the antifungal immune response of S.invicta and increased the susceptibility to M.anisopliae infection compared to controls.Furthermore,RNA interference-based gene silencing elucidated the roles of these immune genes in regulating fungal susceptibility,thus providing vital clues for developing virulent and effective mycoinsecticides using modern genetic engineering tools.展开更多
The filamentous fungus Beauveria bassiana is a natural pathogen of the greater wax moth Galleria mellonella.Infection with this fungus triggered systemic immune response in G.mellonella;nevertheless,the infection was ...The filamentous fungus Beauveria bassiana is a natural pathogen of the greater wax moth Galleria mellonella.Infection with this fungus triggered systemic immune response in G.mellonella;nevertheless,the infection was lethal if spores entered the insect hemocel.We observed melanin deposition in the insect cuticle and walls of air bags,while the invading fungus interrupted tssue continuity.We have shown colonization of muscles,air bags,and finally colonization and complete destruction of the fat body-the main organ responsible for the synthesis of defense molecules in response to infection.This destruction was probably not caused by simple fungal growth,because the fat body was not destroyed during colonization with a human opportunistic pathogen Candida albicans.This may mean that the infecting fungus is able to destroy actively the insect's fat body as part of its virulence mechanism.Finally,we were unable to reduce the extremely high virulence of B.bassiana against G.mellonella by priming of larvae with thermally inactivated fungal spores.展开更多
宫颈癌是全球女性第四大恶性肿瘤,其发生发展与高危型人乳头瘤病毒(high-risk human papillomavirus, HR-HPV)持续感染密切相关,本质是病原(HR-HPV)与宿主(宫颈组织及免疫系统)长期互作失衡的结果。γδ T细胞作为固有免疫与适应性免疫...宫颈癌是全球女性第四大恶性肿瘤,其发生发展与高危型人乳头瘤病毒(high-risk human papillomavirus, HR-HPV)持续感染密切相关,本质是病原(HR-HPV)与宿主(宫颈组织及免疫系统)长期互作失衡的结果。γδ T细胞作为固有免疫与适应性免疫的“桥梁细胞”,以不依赖经典MHC分子的抗原识别模式,在黏膜组织免疫监视中发挥独特作用,其亚群因组织分布、抗原识别谱及功能特性的差异,在HR-HPV感染清除及宫颈癌发生发展中扮演不同角色。本研究从病原-宿主互作核心机制出发,深入分析当前γδ T细胞亚群在宫颈癌免疫监视中的作用及挑战,为宫颈癌的免疫防治提供病原生物学视角的理论依据与研究方向。展开更多
Herein based on literature available a hypothesis is provided about molecular basis for initial events in establishment interactions.This hypothesis asserts that:"recognition and interaction that occur between or...Herein based on literature available a hypothesis is provided about molecular basis for initial events in establishment interactions.This hypothesis asserts that:"recognition and interaction that occur between organisms is prearranged.There are membrane receptors with or without soluble components derived from the respective organisms that bridge specific interactions".Organisms'prearranged recognition theory(OPRT)can be specifically applied to host-microbe interactions where most microbes are coated(opsonised)by soluble components(opsonins)from the host,but there are also some microbes that can bypass host opsonization expressing receptors for the host cells or secreting host’s opsonin-like molecules.The receptors involved in organism's interactions,their specificity and repertoire depend on saccharides from glycoproteins,glycolipids,and polysaccharides(glycans)which are abundant extracellular components.Based in OPRT is possible to explain species-specific interactions and several other phenomena,such as hyper-infectivity,tissue tropism,differential sensitivity to disease depending on type O-blood,and tumoral cell promiscuity.The lipid raft domain in cellular membrane is proposed as the main location where interactions will trigger cellular responses.Possible scientific and biotechnology applications and alternative routes to modify organism's interactions and consequences are discussed.It is a novel hypothesis regarding the degree to which an organism's interactions are prearranged and the role of saccharides epitopes.展开更多
Klebsiella pneumoniae infections(KPIs),particularly carbapenem-resistant Klebsiella pneumoniae(CRKP),pose significant challenges in liver transplantation(LT)recipients,with high morbidity and mortality.Guo et al’s st...Klebsiella pneumoniae infections(KPIs),particularly carbapenem-resistant Klebsiella pneumoniae(CRKP),pose significant challenges in liver transplantation(LT)recipients,with high morbidity and mortality.Guo et al’s study highlights risk factors,such as elevated day-one alanine aminotransferase levels and prolonged catheterization,and identifies polymyxin B and ceftazidime/avibactam as effective treatments.However,limitations like the absence of pre-transplant colonization data and host-pathogen interaction insights highlight the need for enhanced strategies.Future directions should include routine CRKP colonization surveillance,immune and genomic profiling,and the development of novel therapeutics.By integrating these approaches,we can improve the prevention,diagnosis,and treatment of KPIs in LT patients.展开更多
The COVID-19 pandemic,caused by the newly emerged coronavirus SARS-CoV-2,has resulted in unprecedented global health challenges,including millions of infections and deaths.While the direct effects of the virus are cri...The COVID-19 pandemic,caused by the newly emerged coronavirus SARS-CoV-2,has resulted in unprecedented global health challenges,including millions of infections and deaths.While the direct effects of the virus are critical,the interplay between SARS-CoV-2 and cellular host factors significantly impacts the replication cycle of the virus and the clinical severity of COVID-19.This review provides a comprehensive analysis of hostpathogen interactions,focusing on the functional roles and regulatory mechanisms of SARS-CoV-2 viral proteins.We systematically review the literature to detail how SARS-CoV-2 engages with host cellular machinery,with a specific emphasis on their modulation by E3 ubiquitin ligases.By dissecting these intricate interactions and the impact of E3 ligases on SARS-CoV-2 infection,we aimto uncover novel therapeutic opportunities and strategies to effectively combat COVID-19.展开更多
基金the National Natural Science Foundation of China(31672694,31972836)Fujian Provincial Special Fund for Marine and Fishery Protection and Development(MCZ[2019]062)。
文摘Host-pathogen interactions are highly complex,involving large dynamic changes in gene expression during infection. These interactions are fundamental to understanding anti-infection immunity of hosts, as well as the pathogenesis of pathogens. For bacterial pathogens interacting with animal hosts, timeresolved dual RNA-seq of infected tissue is difficult to perform due to low pathogen load in infected tissue. In this study, an acute infection model of Larimichthys crocea infected by Pseudomonas plecoglossicida was established. The spleens of infected fish exhibited typical symptoms, with a maximum bacterial load at two days post-injection(dpi). Time-resolved dual RNA-seq of infected spleens was successfully applied to study hostpathogen interactions between L. crocea and P.plecoglossicida. The spleens of infected L. crocea were subjected to dual RNA-seq, and transcriptome data were compared with those of noninfected spleens or in vitro cultured bacteria. Results showed that pathogen-host interactions were highly dynamically regulated, with corresponding fluctuations in host and pathogen transcriptomes during infection. The expression levels of many immunogenes involved in cytokine-cytokine receptor,Toll-like receptor signaling, and other immunerelated pathways were significantly up-regulated during the infection period. Furthermore, metabolic processes and the use of oxygen in L. crocea were strongly affected by P. plecoglossicida infection. The WGCNA results showed that the metabolic process was strongly related to the entire immune process.For P. plecoglossicida, the expression levels of motility-related genes and flagellum assemblyrelated genes were significantly up-regulated. The results of this study may help to elucidate the interactions between L. crocea and P.plecoglossicida.
文摘Active host-pathogen interactions take place during infection of human immunodeficiency virus type 1 (HIV-1). Outcomes of these interactions determine the efficiency of viral infection and subsequent disease progression. HIV- infected cells respond to viral invasion with various defensive strategies such as innate, cellular and humoral immune antiviral mechanisms. On the other hand, the virus has also developed various offensive tactics to suppress these host cellular responses. Among many of the viral offensive strategies, HIV-1 viral auxiliary proteins (Tat, Rev, Nef, Vif, Vpr and Vpu) play important roles in the host-pathogen interaction and thus have significant impacts on the outcome of HIV infection. One of the best examples is the interaction of Vif with a host cytidine deaminase APOBEC3G. Although specific roles of other auxiliary proteins are not as well described as Vif-APOBEC3G interaction, it is the goal of this brief review to summarize some of the preliminary findings with the hope to stimulate further discussion and investiga- tion in this exhilarating area of research.
文摘The prognosis of infectious diseases is determined by host-pathogen interactions.Control of pathogens has been the central dogma of treating infectious diseases in modern medicine,but the pathogen-directed medicine is facing significant challenges,including a lack of effective antimicrobials for newly emerging pathogens,pathogen drug resistance,and drug side effects.Here,a mathematic equation(ter-med equation of host-pathogen interactions,HPI-Equation)is developed to dissect the key variables of hostpathogen interactions.It shows that control of pathogens does not necessarily lead to host recov-ery.Instead,a combination of promoting a host’s power of self-healing and balancing immune responses provides the best benefit for host.Moreover,the HPI-Equation elucidates the scientific basis of traditional Chinese medicine(TCM),a host-based medicine that treats infectious diseases by promot-ing self-healing power and balancing immune responses.The importance of self-healing power eluci-dated in the HPIEquation is confirmed by recent studies that the tolerance mechanism,which is discovered in plants and animals and conceptually similar to self-healing power,improves host survival without directly attacking pathogens.In summary,the HPI-Equation describes host-pathogen interac-tions with mathematical logic and precision;it translates the ancient wisdoms of TCM into apprehen-sible modern sciences and opens a new venue for integrating TCM and modern medicine for a future medicine.
文摘Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, Micro RNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.
文摘Bacteria employ diverse immune systems,such as CRISPR-Cas,to fend offphage infections.A recent study un-covered the unprecedented mechanistic features of the Kongming bacterial defense system,which uniquely ex-ploits phage-derived enzymes to synthesize deoxyinosine triphosphate(dITP),thereby triggering host immunity through NAD+depletion.In response,some phages have evolved countermeasures to disrupt dITP synthesis,highlighting the ongoing evolutionary arms race between hosts and pathogens.This discovery not only deepens our understanding of bacterial defense strategies but also paves the way for new insights in biomedical research and synthetic biology.
基金supported by grants from the National Natural Science Foundation of China(32172498 and W2433052)the National Key R&D Program of China(2021YFD1000500)the Natural Science Foundation of Guangdong,China(2023A1515010305)。
文摘The red imported fire ant,Solenopsis invicta Buren,is a highly invasive eusocial insect pest that threatens native biodiversity,agriculture,and human health.The innate immune system and intricate social immune responses of S.invicta pose challenges to the development of effective control strategies.Micro RNAs(mi RNAs)play critical roles in the post-transcriptional regulation of gene expression,which influences various biological processes,including immunity and host-pathogen interactions.While the mi RNA-mediated response of insects to pathogens has been extensively studied in solitary insects,little is known about the innate immune responses of individual members within a colony.To address this gap,we constructed small RNA libraries from Metarhizium anisopliae-infected S.invicta workers and investigated the temporal dynamics of mi RNA-mediated immune responses to the entomopathogen.Several differentially expressed mi RNAs were identified,and they were found to regulate genes involved in the Toll,IMD,and melanization immune pathways.Quantitative real-time PCR(q RT-PCR)was employed to analyze the spatiotemporal dynamics of key mi RNAs/target genes,specifically mi R-71/Mod SP1-Relish and mi R-7/Lysozyme2-Serine protease7.A dual luciferase assay(in vitro)was performed to validate the interactions between mi RNAs and their target genes.Overexpression of mi R-71 and mi R-7(via mi RNA mimics)efficiently suppressed their target genes,impaired the antifungal immune response of S.invicta and increased the susceptibility to M.anisopliae infection compared to controls.Furthermore,RNA interference-based gene silencing elucidated the roles of these immune genes in regulating fungal susceptibility,thus providing vital clues for developing virulent and effective mycoinsecticides using modern genetic engineering tools.
文摘The filamentous fungus Beauveria bassiana is a natural pathogen of the greater wax moth Galleria mellonella.Infection with this fungus triggered systemic immune response in G.mellonella;nevertheless,the infection was lethal if spores entered the insect hemocel.We observed melanin deposition in the insect cuticle and walls of air bags,while the invading fungus interrupted tssue continuity.We have shown colonization of muscles,air bags,and finally colonization and complete destruction of the fat body-the main organ responsible for the synthesis of defense molecules in response to infection.This destruction was probably not caused by simple fungal growth,because the fat body was not destroyed during colonization with a human opportunistic pathogen Candida albicans.This may mean that the infecting fungus is able to destroy actively the insect's fat body as part of its virulence mechanism.Finally,we were unable to reduce the extremely high virulence of B.bassiana against G.mellonella by priming of larvae with thermally inactivated fungal spores.
文摘Herein based on literature available a hypothesis is provided about molecular basis for initial events in establishment interactions.This hypothesis asserts that:"recognition and interaction that occur between organisms is prearranged.There are membrane receptors with or without soluble components derived from the respective organisms that bridge specific interactions".Organisms'prearranged recognition theory(OPRT)can be specifically applied to host-microbe interactions where most microbes are coated(opsonised)by soluble components(opsonins)from the host,but there are also some microbes that can bypass host opsonization expressing receptors for the host cells or secreting host’s opsonin-like molecules.The receptors involved in organism's interactions,their specificity and repertoire depend on saccharides from glycoproteins,glycolipids,and polysaccharides(glycans)which are abundant extracellular components.Based in OPRT is possible to explain species-specific interactions and several other phenomena,such as hyper-infectivity,tissue tropism,differential sensitivity to disease depending on type O-blood,and tumoral cell promiscuity.The lipid raft domain in cellular membrane is proposed as the main location where interactions will trigger cellular responses.Possible scientific and biotechnology applications and alternative routes to modify organism's interactions and consequences are discussed.It is a novel hypothesis regarding the degree to which an organism's interactions are prearranged and the role of saccharides epitopes.
基金Supported by the Second Batch of Social Development Science and Technology Program Projects of Taizhou Science and Technology Bureau in 2023,No.24ywb80.
文摘Klebsiella pneumoniae infections(KPIs),particularly carbapenem-resistant Klebsiella pneumoniae(CRKP),pose significant challenges in liver transplantation(LT)recipients,with high morbidity and mortality.Guo et al’s study highlights risk factors,such as elevated day-one alanine aminotransferase levels and prolonged catheterization,and identifies polymyxin B and ceftazidime/avibactam as effective treatments.However,limitations like the absence of pre-transplant colonization data and host-pathogen interaction insights highlight the need for enhanced strategies.Future directions should include routine CRKP colonization surveillance,immune and genomic profiling,and the development of novel therapeutics.By integrating these approaches,we can improve the prevention,diagnosis,and treatment of KPIs in LT patients.
文摘The COVID-19 pandemic,caused by the newly emerged coronavirus SARS-CoV-2,has resulted in unprecedented global health challenges,including millions of infections and deaths.While the direct effects of the virus are critical,the interplay between SARS-CoV-2 and cellular host factors significantly impacts the replication cycle of the virus and the clinical severity of COVID-19.This review provides a comprehensive analysis of hostpathogen interactions,focusing on the functional roles and regulatory mechanisms of SARS-CoV-2 viral proteins.We systematically review the literature to detail how SARS-CoV-2 engages with host cellular machinery,with a specific emphasis on their modulation by E3 ubiquitin ligases.By dissecting these intricate interactions and the impact of E3 ligases on SARS-CoV-2 infection,we aimto uncover novel therapeutic opportunities and strategies to effectively combat COVID-19.
