Infected Organism Research Articles

Early Cytokine Response After Vaccination with Coxiella Burnetii Phase I in an Infected Herd of Dairy Cattle.

IntroductionCoxiella (C.) burnetii, the aetiological agent of Q fever, is able to modulate the macrophage/T-lymphocyte axis in an infected organism and impair synthesis of monokines and lymphokines.Material and MethodsThe purpose of this research was to determine the levels of the cytokines that play a key role in the response to C. burnetii antigens (IL-1β, IL-2, IL-6, IL-10, IFN-γ and TNF-α) in the serum of animals originating from an infected herd prior to vaccination (day 0) and at 1, 7, and 21 days afterwards.ResultsThe vaccination of animals did not affect the production of IL-6, IL-1β, or IL-2. The serum levels of these cytokines were too low to measure in most of the samples. The initial levels of TNFα, IFNγ, and IL-10 were higher in seropositive than in seronegative animals, although significant differences between seropositive shedders and seropositive nonshedders appeared only in the levels of IFNγ and IL-10. Additionally, the course of the post-vaccination response concerning these two cytokines was different among seronegative nonshedders, seropositive nonshedders, and seropositive shedders.ConclusionIt seems that analysis of the IFNγ and IL-10 concentrations in animal blood serum may have some practical value in an assessment of the health status of seropositive animals and post-vaccination response.

Hepatitis E virus: from the infected organism to the cellular response

HepatitisE virus (HEV) presents a worldwide distribution. In developing countries, hepatitisE, related to HEV1and HEV2, is a waterborne disease. In developed countries, hepatitisE is a zoonotic disease due to HEV3and HEV4. It is mainly transmitted through meat consumption from animal reservoirs such as pig, boar, deer and rabbit. New clinical forms include neurological manifestations that are now clearly associated with HEV3 infection. Recent studies showed that ORF1polyprotein was able to disrupt the innate immune response. It was also shown that ORF2protein exists at least in two forms: a free, glycosylated form and a non-glycosylated form, which assembles to form the capsid. Lastly, it was shown that ORF3protein, involved in the virus egress, acts as a viroporin. New culture systems and animal models have been developed recently, and will be very helpful to complete our understanding of HEV life cycle and pathogenesis.

Exploring the immune response, tolerance and resistance in proliferative kidney disease of salmonids

Proliferative kidney disease (PKD) of salmonids is a disease of economic and environmental concern caused by the myxozoan parasite Tetracapsuloides bryosalmonae. Finer details of the immune repertoire during T. bryosalmonae infection have been elucidated in rainbow trout (Oncorhynchus mykiss). In contrast, there remain many unanswered questions regarding the immune response of the wild fish host in Europe, the brown trout (Salmo trutta) to this parasite. The first aim of this study is to examine the brown trout immune response to T. bryosalmonae and compare it with the published information on rainbow trout as two species that have undergone a different coevolution with the parasite. According to ecoimmunology terminology, infected organisms may manage infection by reducing the damage caused by parasites (tolerance) or by limiting parasite burden (resistance). The second aim of this study is to investigate tolerance/resistance patterns of these species during PKD infection. Our results suggest subtle differences in sequential aspects of the immune response and of immune genes that correlate with parasite intensity for the brown trout, in contrast to rainbow trout, in terms of the B cell response and Th-like interplay that may be linked to PKD pathogenesis. These differences in the immune response also correlate with species-specific differences in tolerance/resistance patterns, in that brown trout had increased tolerance but rainbow trout had greater resistance to infection. The variance in tolerance/resistance investment resulted in a different evolutionary outcome for each host-parasite interaction. A greater exploration of these concepts and an association of immune mechanisms could open an additional gateway for interpreting fish host-parasite interactions.

Interaction between the cellular E3 ubiquitin ligase SIAH-1 and the viral immediate-early protein ICP0 enables efficient replication of Herpes Simplex Virus type 2 in vivo.

Herpes Simplex Virus type 2 (HSV-2) is a neurotropic human pathogen. Upon de novo infection, the viral infected cell protein 0 (ICP0) is immediately expressed and interacts with various cellular components during the viral replication cycle. ICP0 is a multifunctional regulatory protein that has been shown to be important for both efficient viral replication and virus reactivation from latency. In particular, as previously demonstrated in transfected tissue culture models, ICP0 interacts with the cellular E3 ubiquitin ligase SIAH-1, which targets ICP0 for proteasomal degradation. However, the consequence of this virus-host interaction during the establishment of HSV-2 infection in vivo has not yet been elucidated. Here we confirmed that ICP0 of HSV-2 interacts with SIAH-1 via two conserved PxAxVxP amino acid binding motifs. We also demonstrate in vitro that a SIAH-1 binding-deficient HSV-2 strain, constructed by homologous recombination technology, exhibits an attenuated growth curve and impaired DNA and protein synthesis. This attenuated phenotype was also confirmed in an in vivo ocular infection mouse model. Specifically, viral load of the SIAH-1 binding-deficient HSV-2 mutant was significantly reduced in the trigeminal ganglia and brain stem at day 5 and 7 post infection. Our findings indicate that the interplay between ICP0 and SIAH-1 is important for efficient HSV-2 replication in vivo, thereby affecting viral dissemination kinetics in newly infected organisms, and possibly revealing novel targets for antiviral therapy.

THE DYNAMICS OF ORTHOHANTAVIRUS HANTAAN STRAINS REPLICATION ON THE MODEL OF MOUSE PERITONEAL MACROPHAGES

Orthohantaviruses (Orthohantavirus genus, Hantaviridae family) are the causative agents of a widespread natural focal infection in the Russian Federation, hemorrhagic fever with renal syndrome (HFRS). An important role in the persistence of orthohantavirus in reservoir hosts among other immunological responses, as well as in the spread of the virus in the infected organism, is played by infected macrophages, which, along with the vascular endothelium, are the main targets for orthohantaviruses.The aim of our study was to investigate the characteristics of replication of orthohantavirus Hantaan strains isolated from Apodemus mice and detect the influence of different values of multiplicity of infection (MOI) on replication dynamics of orthohantaviruses on cell culture.Materials and methods. We used 4 strains of Hantaan virus, isolated from A. agrarius (n = 2) and A. peninsulae (n = 2), captured in the different areas of Primorsky Krai of Russia. The modeling of infection was performed on the primary cell culture of mouse peritoneal macrophages with different MOI (from 10 to 0.1). The assessing of infection was conducted via indirect fluorescent antibody assay, and results were expressed as rate of antigen- positive cells per all cells in the field of vision. Results. Common dynamics of orthohantavirus infection on this in vitro model was characterized by periodically increased rates of infected cells after 2, 4, 6 и 8 hours post infection (p.i.). Replication of A. agrarius-borne strains was more intensive compare with viruses, isolated from A. peninsulae, in the time point 4 hour p.i. on the background the same MOI the statistically significant difference of rate of antigen-positive cell 24.9 ± 2.38 % vs 15.2 ± 1.87 % (t = 3.20; p = 0.001414) was observed. Additionally, the decrease of MOI was followed by determined decrease of replication effectivity.Conclusion. The results of our study showed the significant phenotyping heterogeneity of orthohantavirus Hantaan strains, isolated from Apodemus mice, resulting in different rates of replication in the culture of mouse peritoneal macrophages.

Why, so far, have epidemics always eventually petered out? Quasispecies theory suggests a (testable!) answer.

In this paper, it is argued that the fact that, so far, even the worst and most far-reaching epidemics-from the Plague of Athens in 430 BC and the Plague of Justinian in 541/542 AD to the Hong Kong Flu from 1968/69-always finally petered out can be explained using Manfred Eigen's quasispecies concept: Indeed, as the infectious agents, while duplicating themselves in the infected organisms, mutate all the time, these infected organisms carry along quite a multitude of mutational variants or-in Manfred Eigen's terms-a whole quasispecies of infectious agents implying that, within that quasispecies, those variants that differ from the wild type may actually serve as some kind of vaccination program when infecting some previously uninfected persons. In this context, some data regarding various recent epidemics will also be illustrated, using Daniel Huson's SplitsTree software tool.

P-29 - Unbiased identification of anthracycline-mediated disease protection mechanisms

Anthracyclines, a class of chemotherapeutic drugs that includes epirubicin, doxorubicin and daunorubicin, induce inflammatory cytokines in an in vitro model of inflammation. In vivo, these drugs are strongly protective in the cecal ligation and puncture (CLP) mouse model of sepsis. Moreover, the DNA damage effector kinase Ataxia Telangiectasia Mutated (ATM) was shown to be activated during anthracycline-mediated protection, which suggested that DNA damage response (DDR) mechanisms are required for disease protection. To identify mechanisms whereby anthracyclines mediate cellular protection we performed RNA sequencing (RNAseq) in immune-responsive primary cells (mouse bone marrow-derived macrophages) stimulated with a pro-inflammatory stimulus. We compared cells pre-treated with two members of the anthracycline family that differed in their capacity to generate DNA damage; we also included etoposide, a DNA damaging drug that, unlike anthracyclines, also generates reactive oxygen species (ROS). An expression profile associated with anthracycline treatment in inflammation was identified and pointed to an NF-kb signature. Other unbiased approaches are currently being explored, including RNAseq in target organs of sepsis and whole genome in vivo targeting of infected model organisms.

Identification and characterization of the Fasciola hepatica sodium- and chloride-dependent taurine transporter.

The parasitic liver fluke Fasciola hepatica infests mainly ruminants, but it can also cause fasciolosis in people, who ingest the metacercariae encysted on plants. The drug of choice to treat fasciolosis is triclabendazole (TBZ), which has been on the market for several decades. This is also true for the other available drugs. Accordingly, drug-resistant flukes have been emerging at an increasing rate making it desirable to identify alternative drug targets. Here, we focused on the fact that adult F. hepatica persists in the hostile environment of the bile ducts of infected organisms. A common way to render bile acids less toxic is to conjugate them to taurine (2-aminoethanesulfonic acid). We cloned a transporter from the solute carrier-6 (SLC6) family, which was most closely related to the GABA-transporter-2 of other organisms. When heterologously expressed, this F. hepatica transporter supported the high-affinity cellular uptake of taurine (KM = 12.0 ± 0.5 μM) but not of GABA. Substrate uptake was dependent on Na+- and Cl- (calculated stoichiometry 2:1). Consistent with the low chloride concentration in mammalian bile, the F. hepatica transporter had a higher apparent affinity for Cl- (EC50 = 14±3 mM) than the human taurine transporter (EC50 = 55±7 mM). We incubated flukes with unconjugated bile acids in the presence and absence of taurine: taurine promoted survival of flukes; the taurine transporter inhibitor guanidinoethansulfonic acid abolished this protective effect of taurine. Based on these observations, we conclude that the taurine transporter is critical for the survival of liver flukes in the bile. Thus, the taurine transporter represents a candidate drug target.

Tunneling Nanotubes as a Novel Route of Cell-to-Cell Spread of Herpesviruses.

Various types of intercellular connections that are essential for communication between cells are often utilized by pathogens. Recently, a new type of cellular connection, consisting of long, thin, actin-rich membrane extensions named tunneling nanotubes (TNTs), has been shown to play an important role in cell-to-cell spread of HIV and influenza virus. In the present report, we show that TNTs are frequently formed by cells infected by an alphaherpesvirus, bovine herpesvirus 1 (BoHV-1). Viral proteins, such as envelope glycoprotein E (gE), capsid protein VP26, and tegument protein Us3, as well as cellular organelles (mitochondria) were detected by immunofluorescence and live-cell imaging of nanotubes formed by bovine primary fibroblasts and oropharynx cells (KOP cells). Time-lapse confocal studies of live cells infected with fluorescently labeled viruses showed that viral particles were transmitted via TNTs. This transfer also occurred in the presence of neutralizing antibodies, which prevented free entry of BoHV-1. We conclude that TNT formation contributes to successful cell-to-cell spread of BoHV-1 and demonstrate for the first time the participation of membrane nanotubes in intercellular transfer of a herpesvirus in live cells.IMPORTANCE Efficient transmission of viral particles between cells is an important factor in successful infection by herpesviruses. Herpesviruses can spread by the free-entry mode or direct cell-to-cell transfer via cell junctions and long extensions of neuronal cells. In this report, we show for the first time that an alphaherpesvirus can also spread between various types of cells using tunneling nanotubes, intercellular connections that are utilized by HIV and other viruses. Live-cell monitoring revealed that viral transmission occurs between the cells of the same type as well as between epithelial cells and fibroblasts. This newly discovered route of herpesviruses spread may contribute to efficient transmission despite the presence of host immune responses, especially after reactivation from latency that developed after primary infection. Long-range communication provided by TNTs may facilitate the spread of herpesviruses between many tissues and organs of an infected organism.

A Novel Energy-Efficient Multi-Sensor Fusion Wake-Up Control Strategy Based on a Biomimetic Infectious-Immune Mechanism for Target Tracking.

A biomimetic distributed infection-immunity model (BDIIM), inspired by the immune mechanism of an infected organism, is proposed in order to achieve a high-efficiency wake-up control strategy based on multi-sensor fusion for target tracking. The resultant BDIIM consists of six sub-processes reflecting the infection-immunity mechanism: occurrence probabilities of direct-infection (DI) and cross-infection (CI), immunity/immune-deficiency of DI and CI, pathogen amount of DI and CI, immune cell production, immune memory, and pathogen accumulation under immunity state. Furthermore, a corresponding relationship between the BDIIM and sensor wake-up control is established to form the collaborative wake-up method. Finally, joint surveillance and target tracking are formulated in the simulation, in which we show that the energy cost and position tracking error are reduced to 50.8% and 78.9%, respectively. Effectiveness of the proposed BDIIM algorithm is shown, and this model is expected to have a significant role in guiding the performance improvement of multi-sensor networks.

IDENTIFIKASI PARASIT PADA IKAN BETOK (Anabas testudieus)

Research on identification of parasitic organism in climbing perch (Anabas testudineus) was carried out. The purpose of the research was to identified parasitic organism which infecting climbing perch including parasitic intensity, prevalency, and coefisien of corelation. The result showed that several organs such as gills and intestine, infected parasitic organism. The parasitic organism are Nematoda, Dactylogyrus sp, and Trichodina sp.

PD35-11 RISK AND PROTECTIVE FACTORS FOR RECURRENT URINARY TRACT INFECTION FOLLOWING PERCUTANEOUS NEPHROLITHOTOMY

You have accessJournal of UrologyStone Disease: Surgical Therapy I1 Apr 2018PD35-11 RISK AND PROTECTIVE FACTORS FOR RECURRENT URINARY TRACT INFECTION FOLLOWING PERCUTANEOUS NEPHROLITHOTOMY Chin-Fong AU, Chung-You Tsai, and Shiu-Dong Chung Chin-Fong AUChin-Fong AU More articles by this author , Chung-You TsaiChung-You Tsai More articles by this author , and Shiu-Dong ChungShiu-Dong Chung More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1722AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Pre-existed urinary tract infection (UTI) is often associated with large nephrolithiasis. This study aims to evaluate the predictors of recurrent UTIs in patients status post percutaneous nephrolithotomy (PCNL). METHODS We retrospectively analyzed the medical records of patients with renal stones and pre-operative UTIs who underwent PCNL in one tertiary hospital from January 2010 to June 2015. Patient's demographics as well as stone composition, infected organism and post-operative recurrent UTIs within 12 months were reviewed. Fisher's exact test and logistic regression were applied for univariate analysis and multivariate analysis respectively in order to determine the predictors of post-operative UTIs. RESULTS A total of 201 patients with pre-existed UTIs and large renal stones who had undergone PCNL were recruited. 118(59%) patients were infection free while 83(41%) patients experienced recurrent UTIs post-operatively. Escherichia coli, Proteus mirabilis and Streptococcus species were the most frequently isolated bacterial organisms pre-operatively in both groups. Using the univariate analysis, significant predictors associated with recurrent UTIs were diabetes mellitus (OR=2.109, 95% CI:1.13-3.93, p=0.019) and stone free (OR=0.482, 95% CI:0.269-0.865, p=0.014). In multivariate logistic regression analysis, stone free (OR=0.39, 95% CI 0.20-0.76, p =0.005), diabetes mellitus (OR=2.44, 95% CI:1.21-4.94, p=0.005), age ≥65 (OR=2.39, 95% CI:1.12-5.12, p=0.025), female gender (OR=2.65, 95% CI:1.21-5.78, p=0.015) were significant predictors for recurrent UTIs. However, hypertension and BMI≥27 were not statistically significant predictors. CONCLUSIONS Stone free was a strong protective factor while diabetes mellitus, age ≥65 and female gender were significant risk factors for post-PCNL recurrent UTI. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e725 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Chin-Fong AU More articles by this author Chung-You Tsai More articles by this author Shiu-Dong Chung More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Erratum to: Shannon Entropy to Evaluate Substitution Rate Variation Among Viral Nucleotide Positions in Datasets of Viral siRNAs.

Next-generation sequencing has opened the door to the reconstruction of viral populations and examination of the composition of mutant spectra in infected cells, tissues, and host organisms. In this chapter we present details on the use of the Shannon entropy method to estimate the site-specific nucleotide relative variability of turnip crinkle virus, a positive (+) stranded RNA plant virus, in a large dataset of short RNAs of Cicer arietinum L., a natural reservoir of the virus. We propose this method as a viral metagenomics tool to provide a more detailed description of the viral quasispecies in infected plant tissue. Viral replicative fitness relates to an optimal composition of variants that provide the molecular basis of virus behavior in the complex environment of natural infections. A complete description of viral quasispecies may have implications in determining fitness landscapes for host-virus coexistence and help to design specific diagnostic protocols and antiviral strategies.

Blood-Stage Plasmodium Berghei ANKA Infection Promotes Hepatic Fibrosis by Enhancing Hedgehog Signaling in Mice

Background/Aims: Malaria is the most deadly parasitic infection in the world, resulting in damage to various organs, including the liver, of the infected organism; however, the mechanism causing this damage in the liver remains unclear. Liver fibrosis, a major characteristic of liver diseases, occurs in response to liver injury and is regulated by a complex network of signaling pathways. Hedgehog (Hh) signaling orchestrates a number of hepatic responses including hepatic fibrogenesis. Therefore, we investigated whether Hh signaling influenced the liver’s response to malarial infection. Methods: Eight-week-old male C57BL/6 mice inoculated with blood containing Plasmodium berghei ANKA (PbA)-infected erythrocytes were sacrificed when the level of parasitemia in the blood reached 10% or 30%, and the livers were collected for biochemical analysis. Liver responses to PbA infection were examined by hematoxylin and eosin staining, real-time polymerase chain reaction, immunohistochemistry and western blot. Results: Severe hepatic injury, such as ballooned hepatocytes, sinusoidal dilatation, and infiltrated leukocytes, was evident in the livers of the malaria-infected mice. Hypoxia was also induced in 30% parasitemia group. With the accumulation of Kupffer cells, inflammation markers, TNF-α, interleukin-1β, and chemokine (C-X-C motif) ligand 1, were significantly upregulated in the infected group compared with the control group. Expression of fibrotic markers, including transforming growth factor-β, α-smooth muscle actin (α-SMA), collagen 1a1, thymosin β4, and vimentin, were significantly higher in the infected groups than in the control group. With increased collagen deposition, hepatic stellate cells expressing α-SMA accumulated in the liver of the PbA-infected mice, whereas those cells were rarely detected in the livers of the control mice. The levels of Hh signaling and Yes-associated protein (YAP), two key regulators for hepatic fibrogenesis, were significantly elevated in the infected groups compared with the control group. Treatment of mice with Hh inhibitor, GDC-0449, reduced hepatic inflammation and fibrogenesis with Hh suppression in PbA-infected mice. Conclusion: Our results demonstrate that HSCs are activated in and Hh and YAP signaling are associated with this process, contributing to increased hepatic fibrosis in malaria-infected livers.

Enteroviruses: Classification, Diseases They Cause, and Approaches to Development of Antiviral Drugs.

The genus Enterovirus combines a portion of small (+)ssRNA-containing viruses and is divided into 10 species of true enteroviruses and three species of rhinoviruses. These viruses are causative agents of the widest spectrum of severe and deadly epidemic diseases of higher vertebrates, including humans. Their ubiquitous distribution and high pathogenici- ty motivate active search to counteract enterovirus infections. There are no sufficiently effective drugs targeted against enteroviral diseases, thus treatment is reduced to supportive and symptomatic measures. This makes it extremely urgent to develop drugs that directly affect enteroviruses and hinder their development and spread in infected organisms. In this review, we cover the classification of enteroviruses, mention the most common enterovirus infections and their clinical man- ifestations, and consider the current state of development of anti-enteroviral drugs. One of the most promising targets for such antiviral drugs is the viral Internal Ribosome Entry Site (IRES). The classification of these elements of the viral mRNA translation system is also examined.

Is microbial infection always harmful

It is possible for microbial infection (including parasitic infection) to disrupt the balance of autoimmune tolerance, result in the dysfunction of immune system, and make the organism encountered with the attack of the autoimmune disease.As one of the common places between foreign antigens and autoantigens, molecular mimicry is believed to play a vital role in the pathogenesis of autoimmune diseases.However, a large number of studies suggest that rather than inducing various symptoms of autoimmune diseases, many infection of microorganisms covered with mimic peptide of the autoantigen may even protect the infected organism from the disease at the level of antibodies or T cells when the analogous antigen invaded again.The present paper reviews the possible prognosis after microbial infection based on molecular mimicry. Key words: Molecular mimicry; Altered peptide ligand; Natural autoantibodies; Nonautoaggressive T cells

Induction of Apoptosis and Subsequent Phagocytosis of Virus-Infected Cells As an Antiviral Mechanism.

Viruses are infectious entities that hijack host replication machineries to produce their progeny, resulting, in most cases, in disease and, sometimes, in death in infected host organisms. Hosts are equipped with an array of defense mechanisms that span from innate to adaptive as well as from humoral to cellular immune responses. We previously demonstrated that mouse cells underwent apoptosis in response to influenza virus infection. These apoptotic, virus-infected cells were then targeted for engulfment by macrophages and neutrophils. We more recently reported similar findings in the fruit fly Drosophila melanogaster, which lacks adaptive immunity, after an infection with Drosophila C virus. In these experiments, the inhibition of phagocytosis led to severe influenza pathologies in mice and early death in Drosophila. Therefore, the induction of apoptosis and subsequent phagocytosis of virus-infected cells appear to be an antiviral innate immune mechanism that is conserved among multicellular organisms. We herein discuss the underlying mechanisms and significance of the apoptosis-dependent phagocytosis of virus-infected cells. Investigations on the molecular and cellular features responsible for this underrepresented virus–host interaction may provide a promising avenue for the discovery of novel substances that are targeted in medical treatments against virus-induced intractable diseases.

Photon Management through Virus-Programmed Supramolecular Arrays.

Photon extraction and capture efficiency is a complex function of the material's composition, its molecular structure at the nanoscale, and the overall organization spanning multiple length scales. The architecture of the material defines the performance; nanostructured features within the materials enhance the energy efficiency. Photon capturing materials are largely produced through lithographic, top-down, manufacturing schemes; however, there are limits to the smallest dimension achievable using this technology. To overcome these technological barriers, a bottom-up nanomanufacturing is pursued. Inspired by the self-programmed assembly of virus arrays in host cells resulting in iridescence of infected organisms, virus-programmed, nanostructured arrays are studied to pave the way for new design principles in photon management and biology-inspired materials science. Using the nanoparticles formed by plant viruses in combination with charged polymers (dendrimers), a bottom-up approach is illustrated to prepare a family of broadband, low-angular dependent antireflection mesoscale layered materials for potential application as photon management coatings. Measurement and theory demonstrate antireflectance and phototrapping properties of the virus-programmed assembly. This opens up new bioengineering principles for the nanomanufacture of coatings and films for use in LED lighting and photovoltaics.

Bacterial Toxins for Cancer Therapy.

Several pathogenic bacteria secrete toxins to inhibit the immune system of the infected organism. Frequently, they catalyze a covalent modification of specific proteins. Thereby, they block production and/or secretion of antibodies or cytokines. Moreover, they disable migration of macrophages and disturb the barrier function of epithelia. In most cases, these toxins are extremely effective enzymes with high specificity towards their cellular substrates, which are often central signaling molecules. Moreover, they encompass the capacity to enter mammalian cells and to modify their substrates in the cytosol. A few molecules, at least of some toxins, are sufficient to change the cellular morphology and function of a cell or even kill a cell. Since many of those toxins are well studied concerning molecular mechanisms, cellular receptors, uptake routes, and structures, they are now widely used to analyze or to influence specific signaling pathways of mammalian cells. Here, we review the development of immunotoxins and targeted toxins for the treatment of a disease that is still hard to treat: cancer.

Tetranychus urticae mites do not mount an induced immune response against bacteria.

The genome of the spider mite Tetranychus urticae, a herbivore, is missing important elements of the canonical Drosophila immune pathways necessary to fight bacterial infections. However, it is not known whether spider mites can mount an immune response and survive bacterial infection. In other chelicerates, bacterial infection elicits a response mediated by immune effectors leading to the survival of infected organisms. In T. urticae, infection by either Escherichia coli or Bacillus megaterium did not elicit a response as assessed through genome-wide transcriptomic analysis. In line with this, spider mites died within days even upon injection with low doses of bacteria that are non-pathogenic to Drosophila. Moreover, bacterial populations grew exponentially inside the infected spider mites. By contrast, Sancassania berlesei, a litter-dwelling mite, controlled bacterial proliferation and resisted infections with both Gram-negative and Gram-positive bacteria lethal to T. urticae. This differential mortality between mite species was absent when mites were infected with heat-killed bacteria. Also, we found that spider mites harbour in their gut 1000-fold less bacteria than S. berlesei. We show that T. urticae has lost the capacity to mount an induced immune response against bacteria, in contrast to other mites and chelicerates but similarly to the phloem feeding aphid Acyrthosiphon pisum. Hence, our results reinforce the putative evolutionary link between ecological conditions regarding exposure to bacteria and the architecture of the immune response.