Objective: To observe human to mouse one way mixed lymphocyte(MLC); And to set up the xeno-grats verse host disease Xeno-graft host disease(XGVHD) model,probing its immunologic mechamism.Methods: Mouse splenic lympho...Objective: To observe human to mouse one way mixed lymphocyte(MLC); And to set up the xeno-grats verse host disease Xeno-graft host disease(XGVHD) model,probing its immunologic mechamism.Methods: Mouse splenic lymphocyte were collected in asepsis and treated by mitomycin as activating cell. Human Peripheral blood lymphocytes (hPBL)were separated and gathered as reacting cell; Mouse splenic lymphocyte and hPBL were mixed to incubate for a week. Destroying recipient (mouse) immune system by total body irradiation (TBI) and intraperitoneal injecting CTX、MTX; Separating and collecting hPBL; Injecting hPBL to mouse by caudal vein. Results; ①HPBL in the experiment groups(mixed mouse lymphocyte) proliferated obviously, the amount of 3H-TdR in corporation increased evidently(P<0.05); The mean percentage of CD 4、CD 8、IgG 、IgM positive cells rose markedly. ②Experiment groups,the hPBL were found in the spleen and kidney tissue, fas protein expressing, we occasionally discovered and apoptosis cells.Conclusion: The human to mouse one-way MLC has obvious lymphocyte proliferation. By these means,we succeed in inducing XGVHD and setting up a XGVHD model.展开更多
Objective: Angiogenesis is a crucial step for tumor growth and progression. Changes of liver angiogenesis (without metastatic invasion) in response to primary tumors are not known. The aim of the study was to investig...Objective: Angiogenesis is a crucial step for tumor growth and progression. Changes of liver angiogenesis (without metastatic invasion) in response to primary tumors are not known. The aim of the study was to investigate the liver angiogenesis in non-metastatic colorectal cancer (CRC). Methods: Human colorectal adenocarcinoma tumors were grown subcutaneously in nude mice. All animals showed tumor growth locally without macroscopic or microscopic evidence of liver metastases. Livers were investigated for their microvessel density (MVD) at different stages of tumor growth (as small, medium, and large-sized tumors). Normal non-tumor-bearing mice served as controls. To assess MVD, two endothelial cell markers (anti-CD34 and -CD31 antibodies), image analysis, and immunofluorescent technique were utilized. Enumeration of positive stained endothelial cells revealed the MVD. Results: Non-metastatic livers showed increased levels of MVD vs. control. Moreover, levels of MVD were higher in small and medium-sized tumor groups versus large sized tumor groups. Conclusion: The present data indicate that angiogenesis in the liver is induced in early-stages of CRC. However, this effect is suppressed with advanced tumor growth. These results provide an additional rationale for including antiangiogenic therapy in the treatment of early stages of CRC.展开更多
Objective To explore the effect of α-galactosyleramide (α-GalCer) on immune reconstitution under acute graft-versus-host disease (aGVHD). Methods BALB/c mice were transplanted with allogeneic C57BL/6 bone marro...Objective To explore the effect of α-galactosyleramide (α-GalCer) on immune reconstitution under acute graft-versus-host disease (aGVHD). Methods BALB/c mice were transplanted with allogeneic C57BL/6 bone marrow cells and splenocytes (both 1 × 10^7) after receiving lethal total-body irradiation, α-GalCer (100 ug/kg) or vehicle (dimethyl- sulfoxide) was administered intraperitoneally immediately after transplantation. The effects of α-GalCer on immune reconstitufion, proliferation of T cells and B cells, hematopoiesis, and thymic microenvironment were assessed. Results The α-GalCer group exhibited higher percentages of CD3^+, CD4^+, CD8^+, B220^+, CD40+, and CD86+cells compared with the vehicle group. The number of colony forming unit per 1000 CD34^+ cells in the et-GalCer group was higher than in the vehicle group (P=0.0012). In vitro proliferation assays showed that the α-GalCer group had higher percentages of CD3^+, CD4^+, CD8^+, and B220^+ cells compared with the vehicle group. As for the results of in vivo proliferation assays, the numbers of CD3^+, CD4^+, CD8^+, and B220^+ cells were higher in the α-GalCer group than in the normal group, especially the number of B220^+ cells (P=0.007). Significant difference was not found in thymocyte count between the α-GalCer group and the vehicle group, nor in the percentages of CD3^+, CD4^+, and CD8^+ cells. Conclusion Administration of tl-GalCer after allogeneic bone marrow transplantation may promote immune reconstitution in the presence of aGVHD.展开更多
Ebola virus infection causes severe hemorrhagic fever in human and non-human primates with high mortality. Viral entry/infection is initiated by binding of glycoprotein GP protein on Ebola virion to host cells, follow...Ebola virus infection causes severe hemorrhagic fever in human and non-human primates with high mortality. Viral entry/infection is initiated by binding of glycoprotein GP protein on Ebola virion to host cells, followed by fusion of virus-cell membrane also mediated by GP. Using an human immunodeficiency virus (HIV)-based pseudotyping system, the roles of 41 Ebola GP1 residues in the receptor-binding domain in viral entry were studied by alanine scanning substitutions. We identified that four residues appear to be involved in protein folding/structure and four residues are important for viral entry. An improved entry interference assay was developed and used to study the role of these residues that are important for viral entry. It was found that R64 and K95 are involved in receptor binding. In contrast, some residues such as I170 are important for viral entry, but do not play a major role in receptor binding as indicated by entry interference assay and/or protein binding data, suggesting that these residues are involved in post-binding steps of viral entry. Furthermore, our results also suggested that Ebola and Marburg viruses share a common cellular molecule for entry.展开更多
[ Objective] The study aimed to lay a foundation for the further studies on function mechanism of NS1 protein in the interspecies transmission of waterfowl influenza virus. [Method] Using the serologic assay and the s...[ Objective] The study aimed to lay a foundation for the further studies on function mechanism of NS1 protein in the interspecies transmission of waterfowl influenza virus. [Method] Using the serologic assay and the specific RT-PCR method, some strains of H9 subtype waterfowl influenza virus were isolated from the 12 to 20 day-old muscovy duck flocks without any clinical symptoms in different areas of Guangdong Province. Four of these strains, including A/duck/ZQ/303/2007(H9N2) (A3 for short), A/Duck/FJ/301/2007 (H9N2) (C1 for short), A/Duck/NH/306/2007(H9N2) ( D6 for short), A/duck/SS/402/2007(H9N2) ( E2 for short), and a strain named A/duck/ZC/2007(H9N2) (L1 for short) from a muscovy duck died of avian influenza virus (AIV), were used for NSl gene cloning and sequencing. Subsequently, the obtained NSl gene sequences were compared with other NS1 sequences registered in GenBank, and the phylogenetic analysis was also conducted. [Result] When compared with the H9N2 AIV NS1 sequences in GenBank, the NSl genes of the four AIV strains A3, C1, 136 and E2 displayed homologies ranging from 99% to 100% at nucleotide level, and 95% to 100% at amino acid level; while the NSl gene of L1 strain displayed homology ranging from 94% to 97% at nucleotide level, and 93% to 98% at amino acid level. The phylogenetic tree demonstrated that A3, C1, D6 and E2 were highly resemblant, and L1 was closest to AY66473 (chicken, 2003). By comparison with the NS1 gene sequences of L1, AF523514 (duck), AY664743 (chicken) and EF155262.1 (quail) using DNAstar, A3, C1, D6 and E.2 presented nucleotide variations at site 21 ( R→Q), 70, 71 ( KE→EG), 86 ( A→S), 124 (V→M) and 225 ( S→N), and amino acid variations at site 21,70, 71 and 86 in dsRNA- dependent protein kinase (PKR) binding domain of NSl gene, which induced the evident variations of antigenic determinant and surface proba- bility plot of NS1 protein. [ Conclusion] This study suggested that the amino acid sequence variation in PKR binding domain of NS1 protein had something to do with the virus pathogenicity.展开更多
The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the ...The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.展开更多
We aimed to access if acute graft-versus-host disease (aGVHD) in liver transplantation recipients of hepatocellular carcinoma (HCC) might develop a graft-versus-tumor effect (GVT) other than immunological damage...We aimed to access if acute graft-versus-host disease (aGVHD) in liver transplantation recipients of hepatocellular carcinoma (HCC) might develop a graft-versus-tumor effect (GVT) other than immunological damage which would benefit prophylaxis of tumor recurrence. Methods: Dynamic observation of 3 cases of liver transplantation recipients of HCC and cirrhosis, which developed manifestations of fever, skin rash, watery diarrhea, pancytopenia and were finally diagnosed as aGVHD. Two of which got recovered from intravenously pulse methylprednisolone, high-dose intravenous immunoglobulin, antibiotics administration simultaneously and promptly withdrawal of oral immunosuppressants. Two survivors were follow-up regularly with biological monitoring and imaging surveillance for tumor recurrence thereafter. Results: Two recipients survived healthily with stable liver graft function and normal serum AFP level and blood routine test. No sign of tumor recurrence was found in repeat imaging examinations for liver graft, lung, brain and other tissue or organs within a period of 96 months and 17 months to date, respectively. Conclusien: Despite of the fatal damage to according organs and tissue, it suggest that aGVHD in liver recipients of HCC may also develop a GVT effect and benefit prophylaxis of tumor recurrence and result in a long-term healthy recipients survival.展开更多
The cholinergic anti-inflammatory pathway (CAP) is a neurophysiological mechanism that regulates the immune system. The CAP inhibits inflammation by suppressing cytokine synthesis via release of acetylcholine in org...The cholinergic anti-inflammatory pathway (CAP) is a neurophysiological mechanism that regulates the immune system. The CAP inhibits inflammation by suppressing cytokine synthesis via release of acetylcholine in organs of the reticuloendothelial system, including the lungs, spleen, liver, kidneys and gastrointestinal tract. Acetylcholine can interact with a 7 nicotinic acetylcholine receptors ( a 7 nAchR) expressed by macrophages and other cytokine producing cells, down-regulate pro-inflammatory cytokine synthesis and prevent tissue damage. Herein is a review of the neurophysiological mechanism in which the CAP regulates inflammatory response, as well as its potential interventional strategy for inflammatory diseases.展开更多
The complex interplay between symbiotic bacteria and host immunity plays a key role in shaping intestinal homeostasis and maintaining host health. Paneth cells, as one of the major producers of antimicrobial peptides ...The complex interplay between symbiotic bacteria and host immunity plays a key role in shaping intestinal homeostasis and maintaining host health. Paneth cells, as one of the major producers of antimicrobial peptides in the intestine under steady-state conditions, play a vital role in regulating intestinal flora. Many studies on inflammatory bowel disease(IBD)-associated genes have put Paneth cells at the center of IBD pathogenesis. In this perspective, we focus on mechanistic studies of different cellular processes in Paneth cells that are regulated by various IBD-associated susceptibility genes, and we discuss the hypothesis that Paneth cells function as the central hub for sensing and regulating intestinal flora in the maintenance of intestinal homeostasis.展开更多
A virus that can cause a global pandemic must be highly adaptive to human conditions.Such adaptation is not likely to have emerged suddenly but,instead,may have evolved step by step with each step favored by natural s...A virus that can cause a global pandemic must be highly adaptive to human conditions.Such adaptation is not likely to have emerged suddenly but,instead,may have evolved step by step with each step favored by natural selection.It is thus necessary to develop a theory about the origin in order to guide the search.Here,we propose such a model whereby evolution occurs in both the virus and the hosts(where the evolution is somatic;i.e.,in the immune system).The hosts comprise three groups–the wild animal hosts,the nearby human population,and farther-away human populations.The theory suggests that the conditions under which the pandemic has initially evolved are:(i)an abundance of wild animals in the place of origin(PL_(0));(ii)a nearby human population of low density;(iii)frequent and long-term animal-human contacts to permit step-by-step evolution;and(iv)a level of herd immunity in the animal and human hosts.In this model,the evolving virus may have regularly spread out of PL_(0) although such invasions often fail,leaving sporadic cases of early infections.The place of the first epidemic(PL_(1)),where humans are immunologically naïve to the virus,is likely a distance away from PL_(0).Finally,this current model is only a first attempt and more theoretical models can be expected to guide the search for the origin of SARS-CoV-2.展开更多
Legionella pneumophila is a facultative intracellular pathogen capable of replicating within a broad range of hosts. One unique feature of this pathogen is the cohort of ca. 300 virulence factors(effectors) delivered ...Legionella pneumophila is a facultative intracellular pathogen capable of replicating within a broad range of hosts. One unique feature of this pathogen is the cohort of ca. 300 virulence factors(effectors) delivered into host cells via its Dot/Icm type IV secretion system. Study of these proteins has produced novel insights into the mechanisms of host function modulation by pathogens, the regulation of essential processes of eukaryotic cells and of immunosurveillance. In this review, we will briefly discuss the roles of some of these effectors in the creation of a niche permissive for bacterial replication in phagocytes and recent advancements in the dissection of the innate immune detection mechanisms by challenging immune cells with L. pneumophila.展开更多
文摘Objective: To observe human to mouse one way mixed lymphocyte(MLC); And to set up the xeno-grats verse host disease Xeno-graft host disease(XGVHD) model,probing its immunologic mechamism.Methods: Mouse splenic lymphocyte were collected in asepsis and treated by mitomycin as activating cell. Human Peripheral blood lymphocytes (hPBL)were separated and gathered as reacting cell; Mouse splenic lymphocyte and hPBL were mixed to incubate for a week. Destroying recipient (mouse) immune system by total body irradiation (TBI) and intraperitoneal injecting CTX、MTX; Separating and collecting hPBL; Injecting hPBL to mouse by caudal vein. Results; ①HPBL in the experiment groups(mixed mouse lymphocyte) proliferated obviously, the amount of 3H-TdR in corporation increased evidently(P<0.05); The mean percentage of CD 4、CD 8、IgG 、IgM positive cells rose markedly. ②Experiment groups,the hPBL were found in the spleen and kidney tissue, fas protein expressing, we occasionally discovered and apoptosis cells.Conclusion: The human to mouse one-way MLC has obvious lymphocyte proliferation. By these means,we succeed in inducing XGVHD and setting up a XGVHD model.
文摘Objective: Angiogenesis is a crucial step for tumor growth and progression. Changes of liver angiogenesis (without metastatic invasion) in response to primary tumors are not known. The aim of the study was to investigate the liver angiogenesis in non-metastatic colorectal cancer (CRC). Methods: Human colorectal adenocarcinoma tumors were grown subcutaneously in nude mice. All animals showed tumor growth locally without macroscopic or microscopic evidence of liver metastases. Livers were investigated for their microvessel density (MVD) at different stages of tumor growth (as small, medium, and large-sized tumors). Normal non-tumor-bearing mice served as controls. To assess MVD, two endothelial cell markers (anti-CD34 and -CD31 antibodies), image analysis, and immunofluorescent technique were utilized. Enumeration of positive stained endothelial cells revealed the MVD. Results: Non-metastatic livers showed increased levels of MVD vs. control. Moreover, levels of MVD were higher in small and medium-sized tumor groups versus large sized tumor groups. Conclusion: The present data indicate that angiogenesis in the liver is induced in early-stages of CRC. However, this effect is suppressed with advanced tumor growth. These results provide an additional rationale for including antiangiogenic therapy in the treatment of early stages of CRC.
基金Supported by National Natural Science Foundation of China (30670898, 30572108)National Basic Research Program of China (973 Program) (2005CB522400)Capital Research Fund for Medical Development (2007-2040)
文摘Objective To explore the effect of α-galactosyleramide (α-GalCer) on immune reconstitution under acute graft-versus-host disease (aGVHD). Methods BALB/c mice were transplanted with allogeneic C57BL/6 bone marrow cells and splenocytes (both 1 × 10^7) after receiving lethal total-body irradiation, α-GalCer (100 ug/kg) or vehicle (dimethyl- sulfoxide) was administered intraperitoneally immediately after transplantation. The effects of α-GalCer on immune reconstitufion, proliferation of T cells and B cells, hematopoiesis, and thymic microenvironment were assessed. Results The α-GalCer group exhibited higher percentages of CD3^+, CD4^+, CD8^+, B220^+, CD40+, and CD86+cells compared with the vehicle group. The number of colony forming unit per 1000 CD34^+ cells in the et-GalCer group was higher than in the vehicle group (P=0.0012). In vitro proliferation assays showed that the α-GalCer group had higher percentages of CD3^+, CD4^+, CD8^+, and B220^+ cells compared with the vehicle group. As for the results of in vivo proliferation assays, the numbers of CD3^+, CD4^+, CD8^+, and B220^+ cells were higher in the α-GalCer group than in the normal group, especially the number of B220^+ cells (P=0.007). Significant difference was not found in thymocyte count between the α-GalCer group and the vehicle group, nor in the percentages of CD3^+, CD4^+, and CD8^+ cells. Conclusion Administration of tl-GalCer after allogeneic bone marrow transplantation may promote immune reconstitution in the presence of aGVHD.
基金National Institutes of Health Grant (AI059570 and AI077767)
文摘Ebola virus infection causes severe hemorrhagic fever in human and non-human primates with high mortality. Viral entry/infection is initiated by binding of glycoprotein GP protein on Ebola virion to host cells, followed by fusion of virus-cell membrane also mediated by GP. Using an human immunodeficiency virus (HIV)-based pseudotyping system, the roles of 41 Ebola GP1 residues in the receptor-binding domain in viral entry were studied by alanine scanning substitutions. We identified that four residues appear to be involved in protein folding/structure and four residues are important for viral entry. An improved entry interference assay was developed and used to study the role of these residues that are important for viral entry. It was found that R64 and K95 are involved in receptor binding. In contrast, some residues such as I170 are important for viral entry, but do not play a major role in receptor binding as indicated by entry interference assay and/or protein binding data, suggesting that these residues are involved in post-binding steps of viral entry. Furthermore, our results also suggested that Ebola and Marburg viruses share a common cellular molecule for entry.
基金Supported by Key Specific Program for Science and Technology of Guangdong Province (2008B020700003 A2007A020400006)~~
文摘[ Objective] The study aimed to lay a foundation for the further studies on function mechanism of NS1 protein in the interspecies transmission of waterfowl influenza virus. [Method] Using the serologic assay and the specific RT-PCR method, some strains of H9 subtype waterfowl influenza virus were isolated from the 12 to 20 day-old muscovy duck flocks without any clinical symptoms in different areas of Guangdong Province. Four of these strains, including A/duck/ZQ/303/2007(H9N2) (A3 for short), A/Duck/FJ/301/2007 (H9N2) (C1 for short), A/Duck/NH/306/2007(H9N2) ( D6 for short), A/duck/SS/402/2007(H9N2) ( E2 for short), and a strain named A/duck/ZC/2007(H9N2) (L1 for short) from a muscovy duck died of avian influenza virus (AIV), were used for NSl gene cloning and sequencing. Subsequently, the obtained NSl gene sequences were compared with other NS1 sequences registered in GenBank, and the phylogenetic analysis was also conducted. [Result] When compared with the H9N2 AIV NS1 sequences in GenBank, the NSl genes of the four AIV strains A3, C1, 136 and E2 displayed homologies ranging from 99% to 100% at nucleotide level, and 95% to 100% at amino acid level; while the NSl gene of L1 strain displayed homology ranging from 94% to 97% at nucleotide level, and 93% to 98% at amino acid level. The phylogenetic tree demonstrated that A3, C1, D6 and E2 were highly resemblant, and L1 was closest to AY66473 (chicken, 2003). By comparison with the NS1 gene sequences of L1, AF523514 (duck), AY664743 (chicken) and EF155262.1 (quail) using DNAstar, A3, C1, D6 and E.2 presented nucleotide variations at site 21 ( R→Q), 70, 71 ( KE→EG), 86 ( A→S), 124 (V→M) and 225 ( S→N), and amino acid variations at site 21,70, 71 and 86 in dsRNA- dependent protein kinase (PKR) binding domain of NSl gene, which induced the evident variations of antigenic determinant and surface proba- bility plot of NS1 protein. [ Conclusion] This study suggested that the amino acid sequence variation in PKR binding domain of NS1 protein had something to do with the virus pathogenicity.
文摘The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.
文摘We aimed to access if acute graft-versus-host disease (aGVHD) in liver transplantation recipients of hepatocellular carcinoma (HCC) might develop a graft-versus-tumor effect (GVT) other than immunological damage which would benefit prophylaxis of tumor recurrence. Methods: Dynamic observation of 3 cases of liver transplantation recipients of HCC and cirrhosis, which developed manifestations of fever, skin rash, watery diarrhea, pancytopenia and were finally diagnosed as aGVHD. Two of which got recovered from intravenously pulse methylprednisolone, high-dose intravenous immunoglobulin, antibiotics administration simultaneously and promptly withdrawal of oral immunosuppressants. Two survivors were follow-up regularly with biological monitoring and imaging surveillance for tumor recurrence thereafter. Results: Two recipients survived healthily with stable liver graft function and normal serum AFP level and blood routine test. No sign of tumor recurrence was found in repeat imaging examinations for liver graft, lung, brain and other tissue or organs within a period of 96 months and 17 months to date, respectively. Conclusien: Despite of the fatal damage to according organs and tissue, it suggest that aGVHD in liver recipients of HCC may also develop a GVT effect and benefit prophylaxis of tumor recurrence and result in a long-term healthy recipients survival.
基金This study was supported by grants from the National Natural Science Foundation of China (No. 30672178, 30872683, 30800437) and the National Basic Research Program of China (No. 2005CB522602).
文摘The cholinergic anti-inflammatory pathway (CAP) is a neurophysiological mechanism that regulates the immune system. The CAP inhibits inflammation by suppressing cytokine synthesis via release of acetylcholine in organs of the reticuloendothelial system, including the lungs, spleen, liver, kidneys and gastrointestinal tract. Acetylcholine can interact with a 7 nicotinic acetylcholine receptors ( a 7 nAchR) expressed by macrophages and other cytokine producing cells, down-regulate pro-inflammatory cytokine synthesis and prevent tissue damage. Herein is a review of the neurophysiological mechanism in which the CAP regulates inflammatory response, as well as its potential interventional strategy for inflammatory diseases.
文摘The complex interplay between symbiotic bacteria and host immunity plays a key role in shaping intestinal homeostasis and maintaining host health. Paneth cells, as one of the major producers of antimicrobial peptides in the intestine under steady-state conditions, play a vital role in regulating intestinal flora. Many studies on inflammatory bowel disease(IBD)-associated genes have put Paneth cells at the center of IBD pathogenesis. In this perspective, we focus on mechanistic studies of different cellular processes in Paneth cells that are regulated by various IBD-associated susceptibility genes, and we discuss the hypothesis that Paneth cells function as the central hub for sensing and regulating intestinal flora in the maintenance of intestinal homeostasis.
基金supported by the National Natural Science Foundation of China (31730046, 91731000, 31900417, and 81972691)Guangdong Basic and Applied Basic Research Foundation (2020B1515020030, 2019A1515010708)the National Key Research and Development Project of China (2020YFC0847000)
文摘A virus that can cause a global pandemic must be highly adaptive to human conditions.Such adaptation is not likely to have emerged suddenly but,instead,may have evolved step by step with each step favored by natural selection.It is thus necessary to develop a theory about the origin in order to guide the search.Here,we propose such a model whereby evolution occurs in both the virus and the hosts(where the evolution is somatic;i.e.,in the immune system).The hosts comprise three groups–the wild animal hosts,the nearby human population,and farther-away human populations.The theory suggests that the conditions under which the pandemic has initially evolved are:(i)an abundance of wild animals in the place of origin(PL_(0));(ii)a nearby human population of low density;(iii)frequent and long-term animal-human contacts to permit step-by-step evolution;and(iv)a level of herd immunity in the animal and human hosts.In this model,the evolving virus may have regularly spread out of PL_(0) although such invasions often fail,leaving sporadic cases of early infections.The place of the first epidemic(PL_(1)),where humans are immunologically naïve to the virus,is likely a distance away from PL_(0).Finally,this current model is only a first attempt and more theoretical models can be expected to guide the search for the origin of SARS-CoV-2.
基金Legionella pathogenesis and immune response is supported by grants R56AI103168K02AI085403 and R21AI105714 from the National Institutes of Health
文摘Legionella pneumophila is a facultative intracellular pathogen capable of replicating within a broad range of hosts. One unique feature of this pathogen is the cohort of ca. 300 virulence factors(effectors) delivered into host cells via its Dot/Icm type IV secretion system. Study of these proteins has produced novel insights into the mechanisms of host function modulation by pathogens, the regulation of essential processes of eukaryotic cells and of immunosurveillance. In this review, we will briefly discuss the roles of some of these effectors in the creation of a niche permissive for bacterial replication in phagocytes and recent advancements in the dissection of the innate immune detection mechanisms by challenging immune cells with L. pneumophila.