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The Lyme disease spirochete Borrelia burgdorferi cycles between immature black-legged ticks (Ixodes scapularis) and vertebrate reservoir hosts, such as rodents. Larval ticks acquire spirochetes from infected hosts, and the resultant nymphs transmit the spirochetes to naïve hosts. This study investigated the impact of immunocompetence and host tissue spirochete load on host-to-tick transmission (HTT) of B. burgdorferi and the spirochete load inside immature I. scapularis ticks. Wild-type (WT) C57BL/6J mice and mice with severe combined immunodeficiency (SCID) were experimentally infected with B. burgdorferi. To measure HTT, WT and SCID mice were repeatedly infested with I. scapularis larvae, and ticks were sacrificed at three different developmental stages: engorged larvae, 1-month-old, and 12-month-old nymphs. The spirochete loads in immature ticks and mouse tissues were estimated using qPCR. In WT mice, HTT decreased from 90% to 65% over the course of the infection, whereas in the SCID mice, HTT was always 100%. Larvae that fed on SCID mice acquired a much larger dose of spirochetes compared to larvae that fed on WT mice. This difference in spirochete load persisted over tick development where nymphs that fed as larvae on SCID mice had significantly higher spirochete loads compared to their WT counterparts. HTT and the tick spirochete loads were strongly correlated with the mouse tissue spirochete loads. Our study shows that the host immune system (e.g., the presence of antibodies) influences HTT of B. burgdorferi and the spirochete load in immature I. scapularis ticks. [ABSTRACT FROM AUTHOR]

Many important aspects of human retroviral infections cannot be fully evaluated using only in vitro systems or unmodified animal models. An alternative approach involves the use of humanized mice, which consist of immunodeficient mice that have been transplanted with human cells and/or tissues. Certain humanized mouse models can support robust infection with human retroviruses including different strains of human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV). These models have provided wide-ranging insights into retroviral biology, including detailed information on primary infection, in vivo replication and pathogenesis, latent/persistent reservoir formation, and novel therapeutic interventions. Here we describe the humanized mouse models that are most commonly utilized to study retroviral infections, and outline some of the important discoveries that these models have produced during several decades of intensive research.

Schistosomiasis, caused by the parasitic flatworms called schistosomes, remains one of the most prevailing parasitic diseases in the world. The prodigious oviposition of female worms after maturity is the main driver of pathology due to infection, yet our understanding about the regulation of development and reproduction of schistosomes is limited. Here, we comparatively profiled the transcriptome of Schistosoma japonicum recovered from SCID and BALB/c mice, which were collected 35 days post-infection, when prominent morphological abnormalities could be observed in schistosomes from SCID mice, by performing RNA-seq analysis. Of the 11,183 identified genes, 62 differentially expressed genes (DEGs) with 39 upregulated and 23 downregulated messenger RNAs (mRNAs) were found in male worms from SCID mice (S_M) vs. male worms from BALB/c mice (B_M), and 240 DEGs with 152 upregulated and 88 downregulated mRNAs were found in female worms from SCID mice (S_F) vs. female worms from BALB/c mice (B_F). We also tested nine DEGs with a relatively higher expression abundance in the gonads of the worms (ovary, vitellaria, or testis), suggesting their potential biological significance in the development and reproduction of the parasites. Gene ontology (GO) enrichment analysis revealed that GO terms such as “microtubule-based process,” “multicellular organismal development,” and “Rho protein signal transduction” were significantly enriched in the DEGs in S_F vs. B_F, whereas GO terms such as “oxidation–reduction process,” “response to stress,” and “response to DNA damage stimulus” were significantly enriched in the DEGs in S_M vs. B_M. These results revealed that the differential expression of some important genes might contribute to the morphological abnormalities of worms in SCID mice. Furthermore, we selected one DEG, the mitochondrial prohibitin complex protein 1 (Phb1), to perform double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) in vivo targeting the worms in BALB/c mice, and we found that it was essential for the growth and reproductive development of both male and female S. japonicum worms. Taken together, these results provided a wealth of information on the differential gene expression profiles of schistosomes from SCID mice when compared with those from BALB/c mice, which were potentially involved in regulating the growth and development of schistosomes. These findings contributed to an understanding of parasite biology and provided a rich resource for the exploitation of antischistosomal intervention targets.

Schistosomiasis, caused by the parasitic flatworms called schistosomes, remains one of the most prevailing parasitic diseases in the world. The prodigious oviposition of female worms after maturity is the main driver of pathology due to infection, yet our understanding about the regulation of development and reproduction of schistosomes is limited. Here, we comparatively profiled the transcriptome of Schistosoma japonicum recovered from SCID and BALB/c mice, which were collected 35 days post-infection, when prominent morphological abnormalities could be observed in schistosomes from SCID mice, by performing RNA-seq analysis. Of the 11,183 identified genes, 62 differentially expressed genes (DEGs) with 39 upregulated and 23 downregulated messenger RNAs (mRNAs) were found in male worms from SCID mice (S_M) vs. male worms from BALB/c mice (B_M), and 240 DEGs with 152 upregulated and 88 downregulated mRNAs were found in female worms from SCID mice (S_F) vs. female worms from BALB/c mice (B_F). We also tested nine DEGs with a relatively higher expression abundance in the gonads of the worms (ovary, vitellaria, or testis), suggesting their potential biological significance in the development and reproduction of the parasites. Gene ontology (GO) enrichment analysis revealed that GO terms such as "microtubule-based process," "multicellular organismal development," and "Rho protein signal transduction" were significantly enriched in the DEGs in S_F vs. B_F, whereas GO terms such as "oxidation–reduction process," "response to stress," and "response to DNA damage stimulus" were significantly enriched in the DEGs in S_M vs. B_M. These results revealed that the differential expression of some important genes might contribute to the morphological abnormalities of worms in SCID mice. Furthermore, we selected one DEG, the mitochondrial prohibitin complex protein 1 (Phb1), to perform double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) in vivo targeting the worms in BALB/c mice, and we found that it was essential for the growth and reproductive development of both male and female S. japonicum worms. Taken together, these results provided a wealth of information on the differential gene expression profiles of schistosomes from SCID mice when compared with those from BALB/c mice, which were potentially involved in regulating the growth and development of schistosomes. These findings contributed to an understanding of parasite biology and provided a rich resource for the exploitation of antischistosomal intervention targets. [ABSTRACT FROM AUTHOR]

The growth and development of schistosome has been affected in the immunodeficient hosts. But it remains unresolved about the molecular mechanisms involved in the development and reproduction regulation of schistosomes. This study tested and compared the metabolic profiles of the male and female Schistosoma japonicum worms collected from SCID mice and BALB/c mice at 5 weeks post infection using liquid chromatography tandem mass spectrometry (LC-MS/MS) platform, in which the worms from SCID mice were the investigated organisms and the worms from BALB/c mice were used as the controls. There were 1015 ion features in ESI+ mode and 342 ion features in ESI- mode were identified after filtration by false discovery rate. Distinct metabolic profiles were found to clearly differentiate both male and female worms in SCID mice from those in BALB/c mice using multivariate modeling methods including the Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). There were more differential metabolites in female worms than in male worms between SCID mice and BALB/c mice. And common and uniquely perturbed metabolites and pathways were identified among male and female worms from SCID mice when compared with BALB/c mice. The enriched metabolite sets of the differential metabolites in male worms between SCID mice and BALB/c mice included bile acid biosynthesis, taurine and hypotaurine metabolism, sphingolipid metabolism, retinol metabolism, purine metabolism, etc. And the enriched metabolite sets of differential metabolites in female worms included retinol metabolism, alpha linolenic acid and linoleic acid metabolism, purine metabolism, sphingolipid metabolism, glutamate metabolism, etc. Further detection and comparison in transcript abundance of genes of the perturbed retinol metabolism and its associated meiosis process in worms identified clues suggesting accumulated retinyl ester and perturbed meiotic process. These findings suggested an association between the schistosome with retarded growth and development in SCID mice and their perturbed metabolites and metabolic pathways, and provided a new insight into the growth and development regulation of S. japonicum worms from the metabolic level, which indicated great clues for discovery of drugs or vaccines against the parasites and disease with more researches.

Objective To study the anti-tumor immune effects of WT1 peptide vaccine in SCID mice with xenografted human monocytic leukemia. Methods Twenty-four hours after intraperitoneal injection of human peripheral blood lymphocytes, the xenograft human monocytic leukemia model in SCID mice was established by subcutaneous inoculation of THP1 cells. The mice were randomly divided into three groups with eight mice in each. Blank control group was vaccinated with incomplete Freund's adjuvant (IAF). Helper T cell epitope group was vaccinated with helper T cell epitopes and IAF. WT1 group was vaccinated with WT1 peptide, helper T cell epitopes and IAF. When the tumor volume grew to 100mm3/ intraperitoneal injection of vaccine components started. The SCID mice were killed 14 days after vaccination. LDH release method was adopted to detect the specific CTL killing activity of spleen cells. Histological characteristics of tumor tissue were observed under microscope after HE staining. Flow cytometry was used to test the levels of peripheral blood CD3 +/CD4+/+T cells, CD3+/+/CD8+/+T cells andCD4+/+CD25+/+ Treg cells. ELISA method was applied to detect the levels of serum immunoglobulin, IL-2, γ- interferon, TGF-β and IL-10. Results The xenograft human monocytic leukemia model was successfully established in SCID mice and tumor developed in all the SCID mice. In WT1 group, the activity of mouse spleen cells on THP1 cells was significantly higher than that in helper T cell epitope group and control group (P<0.05). The mean weight and volume of tumor were significantly lower in WT1 group than in helper T cell epitope group and control group (P <0.05). A large amount of tumor cell degeneration and necrosis was observed under the microscope in WT1 group mice and few tumor cells survived. Peripheral blood levels of CD3+/+/CD4+/+T cells, CD3+/+/ CD8+T cells, IgG, IFN-γ and IL-2 were all higher in WT1 group than in helper T cell epitope group and control group (P<0.05). However, peripheral blood levels of CD4+/+/CD25+/+Treg cells, TGF-β and IL-10 were all lower in WT1 group than in helper T cell epitope group and control group (P <0.05). Conclusion WT1 polypeptide vaccine can effectively produce anti-tumor immunity and kill leukemia cells in SCID mice with exnografted human monocytic leukemia. [ABSTRACT FROM AUTHOR]

The growth and development of schistosome has been affected in the immunodeficient hosts. But it remains unresolved about the molecular mechanisms involved in the development and reproduction regulation of schistosomes. This study tested and compared the metabolic profiles of the male and female Schistosoma japonicum worms collected from SCID mice and BALB/c mice at 5 weeks post infection using liquid chromatography tandem mass spectrometry (LC-MS/MS) platform, in which the worms from SCID mice were the investigated organisms and the worms from BALB/c mice were used as the controls. There were 1015 ion features in ESI+ mode and 342 ion features in ESI- mode were identified after filtration by false discovery rate. Distinct metabolic profiles were found to clearly differentiate both male and female worms in SCID mice from those in BALB/c mice using multivariate modeling methods including the Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). There were more differential metabolites in female worms than in male worms between SCID mice and BALB/c mice. And common and uniquely perturbed metabolites and pathways were identified among male and female worms from SCID mice when compared with BALB/c mice. The enriched metabolite sets of the differential metabolites in male worms between SCID mice and BALB/c mice included bile acid biosynthesis, taurine and hypotaurine metabolism, sphingolipid metabolism, retinol metabolism, purine metabolism, etc. And the enriched metabolite sets of differential metabolites in female worms included retinol metabolism, alpha linolenic acid and linoleic acid metabolism, purine metabolism, sphingolipid metabolism, glutamate metabolism, etc. Further detection and comparison in transcript abundance of genes of the perturbed retinol metabolism and its associated meiosis process in worms identified clues suggesting accumulated retinyl ester and perturbed meiotic process. These findings suggested an association between the schistosome with retarded growth and development in SCID mice and their perturbed metabolites and metabolic pathways, and provided a new insight into the growth and development regulation of S. japonicum worms from the metabolic level, which indicated great clues for discovery of drugs or vaccines against the parasites and disease with more researches. [ABSTRACT FROM AUTHOR]

At present, there is no animal model for smallpox that reflects the weakened immune system in people and can therefore help assess the prophylactic (highly preventive) efficiency of antiviral drugs. To fill in the gap, we have explored the possibility of using outbred immunodeficient SCID mice as a model animal for smallpox with the aid of virolo­gical, histological and electron microscopic and sta­tistical methods. There was no clinical evidence of disease by intranasal infection of mice at a dose of 5.2 log10 PFU (plaque forming units). At the same time, the 50 % infective dose (ID50) of VARV estimated for animals by registering the presence of the virus in their lungs after 4 days post i.n. infection was 3.5 log10 PFU and was relatively similar to that in humans, theoretically determined by identification of the clinical picture of the disease. Virus replication was detected only in the respiratory organs of mice challenged i.n. with VARV at a dose of 5.2 log10 PFU (50 ID50). The values for its concentrations in the lungs and nose resembled those for affected people and well-known animal models (Macaca cynomolgus and ICR mice), respiratorily infected with VARV at similar doses. The existing model animals were not significantly different from SCID mice in the duration of viral presence in the lungs. Moreover, in SCID mice, as in humans and other animal models, similar pathomor- phological changes of inflammatory necrotic nature in the respiratory organs have been reported. Using SCID mice in assessing the prophylactic efficacy of the antiviral drugs NIOCH-14 and ST-246 demonstrated the adequacy of the results obtained to those described in the literature. This opens up the prospect of using SCID mice as an animal model for smallpox to develop antiviral drugs intended for people with severe immuno­suppressive states.

Abstract Severe combined immunodeficiency disease (SCID) mice with human lepidic adenocarcinoma were established by the intrabronchial implantation of fresh surgically resected specimens. Human pulmonary adenocarcinoma tissue from 16 different cases was transplanted into SCID mice, and SCID mouse tumors were established from four of these cases (25%). Among the four tumors, the tumor cells of two SCID mice showed replacement lepidic growth of mouse alveolar structures accompanied by multiple intrapulmonary lesions. Human lung carcinoma cell lines showing lepidic growth are rare and the xenograft models using the SCID mouse model developed in the current study will be useful for analyzing the growth and/or progression patterns and clinical behavior of lepidic adenocarcinoma, the major histological subtype of human carcinoma of the lung. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • We established a novel mouse-tick infection model for Theileria orientalis. • The newly established model was able to produce T. orientalis sporozoites in ticks. • The unique transcriptomics patterns for piroplasms and sporozoites were identified. • ToSPAG was identified as a sporozoite-specific antigen in T. orientalis. Abstract Oriental theileriosis caused by Theileria orientalis is an economically significant disease in cattle farming. The lack of laboratory animal models and in vitro culture systems is a major obstacle in the drive to better understand the biology of this parasite. Notably, research on the sporozoite stage of T. orientalis has rarely been undertaken, although such investigations are of paramount importance for vaccine development based on blocking sporozoite invasion of its host animals. In the present study, we established a mouse-tick infection model for propagating T. orientalis in mice and for producing the sporozoite stage in tick salivary glands. Splenectomized severe combined immunodeficient mice transfused with bovine erythrocytes were infected with T. orientalis. The larval ticks of Haemaphysalis longicornis were then fed on the T. orientalis -infected mice. The piroplasm and sporozoite stages were microscopically observed in the mouse blood and nymphal salivary glands, respectively. The transcriptomics data generated from the piroplasm and sporozoite stages revealed a stage-specific expression pattern for the parasite genes. The mouse-tick infection model and the transcriptomics data it has provided will contribute to a better understanding of T. orientalis biology and will also provide much needed information for the design of effective control measures targeting oriental theileriosis. [ABSTRACT FROM AUTHOR]