A Combination of Deworming and Prime-Boost Vaccination Regimen Restores Efficacy of Vaccination Against Influenza in Helminth-Infected Mice

Helminths still infect a quarter of the human population. They manage to establish chronic infections by downmodulating the immune system of their hosts. Consequently, the immune response of helminth-infected individuals to vaccinations may be impaired as well. Here we study the impact of helminth-induced immunomodulation on vaccination efficacy in the mouse system. We have previously shown that an underlying Litomosoides sigmodontis infection reduced the antibody (Ab) response to anti-influenza vaccination in the context of a systemic expansion of type 1 regulatory T cells (Tr1). Most important, vaccine-induced protection from a challenge infection with the 2009 pandemic H1N1 influenza A virus (2009 pH1N1) was impaired in vaccinated, L. sigmodontis-infected mice. Here, we aim at the restoration of vaccination efficacy by drug-induced deworming. Treatment of mice with Flubendazole (FBZ) resulted in elimination of viable L. sigmodontis parasites in the thoracic cavity after two weeks. Simultaneous FBZ-treatment and vaccination did not restore Ab responses or protection in L. sigmodontis-infected mice. Likewise, FBZ-treatment two weeks prior to vaccination did not significantly elevate the influenza-specific Ig response and did not protect mice from a challenge infection with 2009 pH1N1. Analysis of the regulatory T cell compartment revealed that L. sigmodontis-infected and FBZ-treated mice still displayed expanded Tr1 cell populations that may contribute to the sustained suppression of vaccination responses in successfully dewormed mice. To outcompete this sustained immunomodulation in formerly helminth-infected mice, we finally combined the drug-induced deworming with an improved vaccination regimen. Two injections with the non-adjuvanted anti-influenza vaccine Begripal conferred 60% protection while MF59-adjuvanted Fluad conferred 100% protection from a 2009 pH1N1 infection in FBZ-treated, formerly L. sigmodontis-infected mice. Of note, applying this improved prime-boost regimen did not restore protection in untreated L. sigmodontis-infected mice. In summary our findings highlight the risk of failed vaccinations due to helminth infection.

Hand Gesture Recognition System as Virtual Mouse for HCI

The technique of interaction between human and computer is evolving since the invention of computer technology. The mouse is one of the invention in HCI (human computer interaction) technology. Though wireless are Bluetooth mouse technology is invented still, that technology is not completely device free. A Bluetooth mouse has the requirement of battery power it requires extra power supply. Presence of extra devices in a mouse increases the difficulty level of more hardware components. The proposed mouse system is outside this limitation. This paper proposes a virtual mouse system using colored hand glove based on HCI using computer vision and hand gestures. Gestures captured with a webcam on processed with color segmentation, detection technique and feature extraction. The user will be allowed to control some of the computer cursor functions with a colored glove on the hand. Primarily, a user can perform with their fingers, scrolling up or down using their hands in different gestures. This system captures frames using a webcam or built-in cam it is based on the camera quality. So the usage of colored glove mouse system eliminates device dependency in order to use a mouse. Keywords: HCI(human computer interaction), colored hand glove , gestures

New insights into the microbiota of wild mice

Laboratory mice have long been an invaluable tool in biomedical science and have made significant contributions in research into life-threatening diseases. However, the translation of research results from mice to humans often proves difficult due to the incomplete nature of laboratory animal-based research. Hence, there is increasing demand for complementary methods or alternatives to laboratory mice that can better mimic human physiological traits and potentially bridge the translational research gap. Under these circumstances, the natural/naturalized mice including “wild”, “dirty”, “wildling”, and “wilded” systems have been found to better reflect some aspects of human pathophysiology. Here, we discuss the pros and cons of the laboratory mouse system and contemplate how wild mice and wild microbiota are able to help in refining such systems to better mimic the real-world situation and contribute to more productive translational research.

Development of CNN-based Virtual Mouse

The technique of building a process of interaction between human and computer is evolving since the invention of technology. The mouse is a superb invention in HCI (Human-Computer Interaction) technology. Though wireless mouse technology is invented still, that technology isn't completely device free. A Bluetooth mouse has the need of battery power and connecting dongle. The proposed mouse system is beyond this limitation. This paper proposes a virtual mouse system supported HCI using computer vision and hand gestures. Gestures captured with a built-in camera or webcam and processed by a Convolutional Neural Network Model for classification among the desired mouse operations. The users are going to be allowed to regulate a number of the pc cursor functions with their hand gestures. Primarily, a user can perform left clicks, right clicks, and double clicks, scrolling up or down using their hand in several gestures. This technique captures frames employing a webcam or built-in cam and processes the frames to make them track-able and then recognizes different gestures made by users and perform the mouse functions. Therefore the proposed mouse system eliminates device dependency so as to use a mouse.

Sexual Dimorphism of the Neuroimmunoendocrine Response in the Spleen During a Helminth Infection: A New Role for an Old Player?

The interaction of the nervous, immune, and endocrine systems is crucial in the maintenance of homeostasis in vertebrates, and vital in mammals. The spleen is a key organ that regulates the neuroimmunoendocrine system. The Taenia crassiceps mouse system is an excellent experimental model to study the complex host-parasite relationship, particularly sex-associated susceptibility to infection. The aim of the present study was to determine the changes in neurotransmitters, cytokines, sex steroids, and sex-steroid receptors in the spleen of cysticercus-infected male and female mice, and the association of these different components with whole parasite counts. We found that parasite load was higher in female in comparison to male mice. The levels of the neurotransmitter epinephrine were significantly decreased in infected male animals. The expression of IL-2 and IL-4 in the spleen was markedly increased in infected mice; however, the expression of Interleukin (IL)-10 and Interferon (IFN)-γ decreased. We also observed sex-associated differences between non-infected and infected mice. Interestingly, the data show that estradiol levels increased in infected males but decreased in females. Our studies provide evidence that infection leads to changes on neuroimmunoendocrine molecules in the spleen during infection. These changes are dimorphic and impact the establishment, growth, and reproduction of T. crassiceps. Our findings support the key role of the neuroimmune network in determining sex-associated susceptibility to the helminth parasite.

Visualization of X chromosome reactivation in mouse primordial germ cells in vivo

ABSTRACT X chromosome inactivation (XCI), determined during development, remains stable after embryonic cell divisions. However, primordial germ cells (PGCs) are exceptions in that XCI is reprogrammed and inactivated X chromosomes are reactivated. Although interactions between PGCs and somatic cells are thought to be important for PGC development, little is known about them. Here, we performed imaging of X chromosome reactivation (XCR) using the ‘Momiji’ mouse system, which can monitor the X chromosome's inactive and active states using two color fluorescence reporter genes, and investigated whether interactions would affect XCR in PGCs. Based on their expression levels, we found that XCR of the Pgk1 locus began at embryonic day (E)10.5 and was almost complete by E13.5. During this period, PGCs became distributed uniformly in the genital ridge, proliferated, and formed clusters; XCR progressed accordingly. In addition, XCR of the Pgk1 locus preceded that of the Hprt locus, indicating that the timing of epigenetic memory erasure varied according to the locus of each of these X-linked genes. Our results indicate that XCR proceeds along with the proliferation of PGCs clustered within the genital ridge. This article has an associated First Person interview with the first author of the paper.

Gene expression in Staphylococcus aureus skin infection

Gene expression in Staphylococcus aureus changes during infection to survive its host. Therefore, to find new strategies to combat staphylococcal infections, it is important to understand the mechanisms that this pathogen uses to adapt to its host and how the host responds to the presence of staphylococcal cells. We have reviewed two studies of gene expression in Staphylococcus aureus during skin infections, one study using a rabbit skin infection model and the other study using a diabetic skin infection model in mice. We compared the two gene expression profiles to find similarities and differences. Many genes did not show any differences in gene expression in S. aureus during the skin infection compared to the control groups. However,19 genes were upregulated in both systems include chaperones (e.g., groES, groEL, grpE, dnaK9), sodM, hrcA, sbi, and the gene encoding a cadmium-exporting ATPase protein. Also, four genes were downregulated in both systems including a gene that encodes a hydrolase and three genes for hypothetical proteins. Also, there was a group of genes expressed in different ways in the two systems. The gene expression of sarU, transcriptional regulators of the LysR family, Cro family, crp family, TetR family, tenA, and many hypothetical proteins were upregulated in the rabbit system but downregulated in the mouse system. The genes rps, rpl, rpm, and several others involved, for example, in translation and transcription were downregulated in the rabbit system but upregulated in the mouse system. Many genes that showed significant changes in overall gene expression in the rabbit model were unaffected in the mouse model. For example, in the rabbit skin infection model increased important gene regulators like agr and sarV, while some stress-response genes (e.g., sigB and lexA) were downregulated. The gene expression of several staphylococcal genes encoding virulence factors such as fibronectin-binding proteins, hemolysins, coagulases, complement inhibitory proteins, Emp, and many exotoxins were upregulated while clumping factor A was downregulated. Besides, some genes showed expression changes in the mouse model, but not in the rabbit model. For example, sarA, rot, ecb, ctsR, spx, many ribosomal proteins, and hypothetical proteins increased, while cap5k, lysE, rusA, and many hypothetical proteins decreased in the mouse model but they were unaffected in the rabbit model. On the other hand, the host responded to the S. aureus infection by inducing the expression of genes encoding host inflammatory cytokines, receptors, genes associated with neutrophil adhesion and migration, inflammation, and immune cell trafficking. In conclusion, the level of gene expression changed both in the pathogen and the host during the skin infection. The information of gene expression can make significant contributions to understand which genes are involved in the infection process, which can be targeted for antimicrobial chemotherapy.

Intrauterine IPEX

IPEX is one of the few Inborn Errors of Immunity that may manifest in the fetal period, and its intrauterine forms certainly represent the earliest human autoimmune diseases. Here, we review the clinical, histopathologic, and genetic findings from 21 individuals in 11 unrelated families, with nine different mutations, described as cases of intrauterine IPEX. Recurrent male fetal death (multigenerational in five families) due to hydrops in the midsemester of pregnancy was the commonest presentation (13/21). Noteworthy, in the affected families, there were only fetal- or perinatal-onset cases, with no affected individuals presenting milder forms with later-life manifestation. Most alive births were preterm (5/6). Skin desquamation and intrauterine growth restriction were observed in part of the cases. Fetal ultrasonography showed hyperechoic bowel or dilated bowel loops in the five cases with available imaging data. Histopathology showed multi-visceral infiltrates with T lymphocytes and other cells, including eosinophils, the pancreas being affected in most of the cases (11/21) and as early as at 18 weeks of gestational age. Regarding the nine FOXP3 mutations found in these cases, six determine protein truncation and three predictably impair protein function. Having found distinct presentations for the same FOXP3 mutation in different families, we resorted to the mouse system and showed that the scurfy mutation also shows divergent severity of phenotype and age of death in C57BL/6 and BALB/c backgrounds. We also reviewed age-of-onset data from other monogenic Tregopathies leading to IPEX-like phenotypes. In monogenic IPEX-like syndromes, the intrauterine onset was only observed in two kindreds with IL2RB mutations, with two stillbirths and two premature neonates who did not survive. In conclusion, intrauterine IPEX cases seem to constitute a particular IPEX subgroup, certainly with the most severe clinical presentation, although no strict mutation-phenotype correlations could be drawn for these cases.

Co-activation of NF-κB and MYC renders cancer cells addicted to IL6 for survival and phenotypic stability

SummaryNF-κB and MYC are found co-deregulated in human B and plasma-cell cancers. In physiology, NF-κB is necessary for terminal B-to-plasma cell differentiation, whereas MYC repression is required. It is thus unclear if NF-κB/MYC co-deregulation is developmentally compatible in carcinogenesis and/or impacts cancer cell differentiation state, possibly uncovering unique sensitivities. Using a mouse system to trace cell lineage and oncogene activation we found that NF-κB/MYC co-deregulation originated cancers with a plasmablast-like phenotype, alike human plasmablastic-lymphoma and was linked to t(8;14)[MYC-IGH] multiple myeloma. Notably, in contrast to NF-κB or MYC activation alone, co-deregulation rendered cells addicted to IL6 for survival and phenotypic stability. We propose that conflicting oncogene-driven differentiation pressures can be accommodated at a cost in poorly-differentiated cancers.SignificanceOur studies improve the understanding of cancer pathogenesis by demonstrating that co-deregulation of NF-κB and MYC synergize in forming a cancer with a poorly-differentiated state. The cancers in the mouse system share features with human Plasmablastic lymphoma that has a dismal prognosis and no standard of care, and with t(8;14)[MYC-IGH] Multiple myeloma, which is in overall resistant to standard therapy. Notably, we found that NF-κB and MYC co-deregulation uniquely render cells sensitive to IL6 deprivation, providing a road-map for patient selection. Because of the similarity of the cancers arising in the compound mutant mouse model with that of human Plasmablastic lymphoma and t(8;14)[MYC-IGH] Multiple myeloma, this model could serve in preclinical testing to investigate novel therapies for these hard-to-treat diseases.HighlightsNF-κB and MYC co-activation originates (pre)plasmablast-like cancerNF-κB/MYC+ renders cancer cells addicted to IL6 for survival and phenotypic stabilityNF-κB/MYC+ cancers are alike a fraction of human plasmablastic lymphomat(8;14)[MYC-IGH] multiple myeloma is linked to a NF-κB/MYC co-activation signature