Parasites and immunotherapy: with or against?

Immunotherapy is a sort of therapy in which antibody or antigen administrates to the patient in order to treat or reduce the severity of complications of disease. This kind of treatment practiced in a wide variety of diseases including infectious diseases, autoimmune disorders, cancers and allergy. Successful and unsuccessful immunotherapeutic strategies have been practiced in variety of parasitic infections. On the other hand parasites or parasite antigens have also been considered for immunotherapy against other diseases such as cancer, asthma and multiple sclerosis. In this paper immunotherapy against common parasitic infections, and also immunotherapy of cancer, asthma and multiple sclerosis with parasites or parasite antigens have been reviewe

Cathelicidin-like Helminth Defence Molecules (HDMs) Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation

Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in the defence against infectious agents of mammals, possessing both bactericidal and immune-modulatory activities. We have identified a novel family of molecules secreted by helminth parasites (helminth defence molecules; HDMs) that exhibit similar structural and biochemical characteristics to the HDPs. Here, we have analyzed the functional activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian HDPs the helminth-derived HDMs show no antimicrobial activity and are non-cytotoxic to mammalian cells (macrophages and red blood cells). However, both the mammalian- and helminth-derived peptides suppress the activation of macrophages by microbial stimuli and alter the response of B cells to cytokine stimulation. Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved to regulate the immune responses of their mammalian hosts by retaining potent immune modulatory properties without causing deleterious cytotoxic effects. © 2013 Thivierge et al

Bone mineral density in Jamaican men on androgen deprivation therapy for prostate cancer

<p>Abstract</p> <p>Background</p> <p>Androgen deprivation therapy (ADT) has been reported to reduce the bone mineral density (BMD) in men with prostate cancer (CaP). However, Afro-Caribbeans are under-represented in most studies. The aim was to determine the effect of androgen deprivation therapy (ADT) on the bone mineral density (BMD) of men with prostate cancer in Jamaica.</p> <p>Methods</p> <p>The study consisted of 346 Jamaican men, over 40 years of age: 133 ADT treated CaP cases (group 1), 43 hormone-naïve CaP controls (group 2) and 170 hormone naïve controls without CaP (group 3). Exclusion criteria included metastatic disease, bisphosphonate therapy or metabolic disease affecting BMD. BMD was measured with a calcaneal ultrasound and expressed in S.D. units relative to young adult men (T score), according to the World Health Organization definition. Patient weight, height and BMI were assessed.</p> <p>Results</p> <p>Mean ± sd, age of patients in group 1 (75± 7.4 yrs) was significantly greater than groups 2 and 3 (67 ± 8.1 yrs; 65±12.0 yrs). There was no significant difference in weight and BMI between the 3 groups. . The types of ADT (% of cases, median duration in months with IQR) included LHRH (Luteinizing hormone releasing hormone) analogues (28.6%, 17.9, IQR 20.4), oestrogens (9.8%, 60.5, IQR 45.6) anti-androgens (11.3%, 3.3, IQR 15.2) and orchiectomy (15.7%, 43.4, IQR 63.9). Unadjusted t score of group 1, mean ± sd, (-1.6± 1.5) was significantly less than group 2 (-0.9±1.1) and group 3 (-0.7±1.4), p <0.001. Ninety three (69.9%), 20 (45%) and 75 (42%) of patients in groups 1, 2 and 3 respectively were classified as either osteopenic or osteoporotic (p<0.001). Adjusting for age, there was a significant difference in t scores between groups 1 and 2 as well as between groups 1 and 3 (p<0.001). Compared with oestrogen therapy and adjusting for duration of therapy, the odds of low bone mineral density (osteopenia or osteoporosis) with LHRH analogue was 4.5 (95%CI, 14.3 to 3.4); with anti-androgens was 5.9 (95%CI, 32.7 to 5); with orchiectomy was 7.3 (95%CI, 30 to 5.8) and multiple drugs was 9.2 ((95%CI, 31 to 7.1).</p> <p>Conclusions</p> <p>ADT is associated with lower BMD in Jamaican men on hormonal therapy for prostate cancer.</p

Pyrokinin β-Neuropeptide Affects Necrophoretic Behavior in Fire Ants (S. invicta), and Expression of β-NP in a Mycoinsecticide Increases Its Virulence

Fire ants are one of the world's most damaging invasive pests, with few means for their effective control. Although ecologically friendly alternatives to chemical pesticides such as the insecticidal fungus Beauveria bassiana have been suggested for the control of fire ant populations, their use has been limited due to the low virulence of the fungus and the length of time it takes to kill its target. We present a means of increasing the virulence of the fungal agent by expressing a fire ant neuropeptide. Expression of the fire ant (Solenopsis invicta) pyrokinin β -neuropeptide (β-NP) by B. bassiana increased fungal virulence six-fold towards fire ants, decreased the LT50, but did not affect virulence towards the lepidopteran, Galleria mellonella. Intriguingly, ants killed by the β-NP expressing fungus were disrupted in the removal of dead colony members, i.e. necrophoretic behavior. Furthermore, synthetic C-terminal amidated β-NP but not the non-amidated peptide had a dramatic effect on necrophoretic behavior. These data link chemical sensing of a specific peptide to a complex social behavior. Our results also confirm a new approach to insect control in which expression of host molecules in an insect pathogen can by exploited for target specific augmentation of virulence. The minimization of the development of potential insect resistance by our approach is discussed

Revised Lithostratigraphy of the Sonsela Member (Chinle Formation, Upper Triassic) in the Southern Part of Petrified Forest National Park, Arizona

BACKGROUND: Recent revisions to the Sonsela Member of the Chinle Formation in Petrified Forest National Park have presented a three-part lithostratigraphic model based on unconventional correlations of sandstone beds. As a vertebrate faunal transition is recorded within this stratigraphic interval, these correlations, and the purported existence of a depositional hiatus (the Tr-4 unconformity) at about the same level, must be carefully re-examined. METHODOLOGY/PRINCIPAL FINDINGS: Our investigations demonstrate the neglected necessity of walking out contacts and mapping when constructing lithostratigraphic models, and providing UTM coordinates and labeled photographs for all measured sections. We correct correlation errors within the Sonsela Member, demonstrate that there are multiple Flattops One sandstones, all of which are higher than the traditional Sonsela sandstone bed, that the Sonsela sandstone bed and Rainbow Forest Bed are equivalent, that the Rainbow Forest Bed is higher than the sandstones at the base of Blue Mesa and Agate Mesa, that strata formerly assigned to the Jim Camp Wash beds occur at two stratigraphic levels, and that there are multiple persistent silcrete horizons within the Sonsela Member. CONCLUSIONS/SIGNIFICANCE: We present a revised five-part model for the Sonsela Member. The units from lowest to highest are: the Camp Butte beds, Lot's Wife beds, Jasper Forest bed (the Sonsela sandstone)/Rainbow Forest Bed, Jim Camp Wash beds, and Martha's Butte beds (including the Flattops One sandstones). Although there are numerous degradational/aggradational cycles within the Chinle Formation, a single unconformable horizon within or at the base of the Sonsela Member that can be traced across the entire western United States (the "Tr-4 unconformity") probably does not exist. The shift from relatively humid and poorly-drained to arid and well-drained climatic conditions began during deposition of the Sonsela Member (low in the Jim Camp Wash beds), well after the Carnian-Norian transition

Individual Attachment Style Modulates Human Amygdala and Striatum Activation during Social Appraisal

Adult attachment style refers to individual personality traits that strongly influence emotional bonds and reactions to social partners. Behavioral research has shown that adult attachment style reflects profound differences in sensitivity to social signals of support or conflict, but the neural substrates underlying such differences remain unsettled. Using functional magnetic resonance imaging (fMRI), we examined how the three classic prototypes of attachment style (secure, avoidant, anxious) modulate brain responses to facial expressions conveying either positive or negative feedback about task performance (either supportive or hostile) in a social game context. Activation of striatum and ventral tegmental area was enhanced to positive feedback signaled by a smiling face, but this was reduced in participants with avoidant attachment, indicating relative impassiveness to social reward. Conversely, a left amygdala response was evoked by angry faces associated with negative feedback, and correlated positively with anxious attachment, suggesting an increased sensitivity to social punishment. Secure attachment showed mirror effects in striatum and amygdala, but no other specific correlate. These results reveal a critical role for brain systems implicated in reward and threat processing in the biological underpinnings of adult attachment style, and provide new support to psychological models that have postulated two separate affective dimensions to explain these individual differences, centered on the ventral striatum and amygdala circuits, respectively. These findings also demonstrate that brain responses to face expressions are not driven by facial features alone but determined by the personal significance of expressions in current social context. By linking fundamental psychosocial dimensions of adult attachment with brain function, our results do not only corroborate their biological bases but also help understand their impact on behavior

Cryptosporidium parvum, a potential cause of colic adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Cryptosporidiosis represents a major public health problem. This infection has been reported worldwide as a frequent cause of diarrhoea. Particularly, it remains a clinically significant opportunistic infection among immunocompromised patients, causing potentially life-threatening diarrhoea in HIV-infected persons. However, the understanding about different aspects of this infection such as invasion, transmission and pathogenesis is problematic. Additionally, it has been difficult to find suitable animal models for propagation of this parasite. Efforts are needed to develop reproducible animal models allowing both the routine passage of different species and approaching unclear aspects of <it>Cryptosporidium </it>infection, especially in the pathophysiology field.</p> <p>Results</p> <p>We developed a model using adult severe combined immunodeficiency (SCID) mice inoculated with <it>Cryptosporidium parvum </it>or <it>Cryptosporidium muris </it>while treated or not with Dexamethasone (Dex) in order to investigate divergences in prepatent period, oocyst shedding or clinical and histopathological manifestations. <it>C. muris</it>-infected mice showed high levels of oocysts excretion, whatever the chemical immunosuppression status. Pre-patent periods were 11 days and 9.7 days in average in Dex treated and untreated mice, respectively. Parasite infection was restricted to the stomach, and had a clear preferential colonization for fundic area in both groups. Among <it>C. parvum</it>-infected mice, Dex-treated SCID mice became chronic shedders with a prepatent period of 6.2 days in average. <it>C. parvum</it>-inoculated mice treated with Dex developed glandular cystic polyps with areas of intraepithelial neoplasia, and also with the presence of intramucosal adenocarcinoma.</p> <p>Conclusion</p> <p>For the first time <it>C. parvum </it>is associated with the formation of polyps and adenocarcinoma lesions in the gut of Dex-treated SCID mice. Additionally, we have developed a model to compare chronic <it>muris </it>and <it>parvum </it>cryptosporidiosis using SCID mice treated with corticoids. This reproducible model has facilitated the evaluation of clinical signs, oocyst shedding, location of the infection, pathogenicity, and histopathological changes in the gastrointestinal tract, indicating divergent effects of Dex according to <it>Cryptosporidium </it>species causing infection.</p

Nucleosomes Containing Methylated DNA Stabilize DNA Methyltransferases 3A/3B and Ensure Faithful Epigenetic Inheritance

How epigenetic information is propagated during somatic cell divisions is still unclear but is absolutely critical for preserving gene expression patterns and cellular identity. Here we show an unanticipated mechanism for inheritance of DNA methylation patterns where the epigenetic mark not only recruits the catalyzing enzyme but also regulates the protein level, i.e. the enzymatic product (5-methylcytosine) determines the level of the methylase, thus forming a novel homeostatic inheritance system. Nucleosomes containing methylated DNA stabilize de novo DNA methyltransferases, DNMT3A/3B, allowing little free DNMT3A/3B enzymes to exist in the nucleus. Stabilization of DNMT3A/3B on nucleosomes in methylated regions further promotes propagation of DNA methylation. However, reduction of cellular DNA methylation levels creating more potential CpG substrates counter-intuitively results in a dramatic decrease of DNMT3A/3B proteins due to diminished nucleosome binding and subsequent degradation of the unstable free proteins. These data show an unexpected self-regulatory inheritance mechanism that not only ensures somatic propagation of methylated states by DNMT1 and DNMT3A/3B enzymes but also prevents aberrant de novo methylation by causing degradation of free DNMT3A/3B enzymes

Cell-Specific DNA Methylation Patterns of Retina-Specific Genes

Many studies have demonstrated that epigenetic mechanisms are important in the regulation of gene expression during embryogenesis, gametogenesis, and other forms of tissue-specific gene regulation. We sought to explore the possible role of epigenetics, specifically DNA methylation, in the establishment and maintenance of cell type-restricted gene expression in the retina. To assess the relationship between DNA methylation status and expression level of retinal genes, bisulfite sequence analysis of the 1000 bp region around the transcription start sites (TSS) of representative rod and cone photoreceptor-specific genes and gene expression analysis were performed in the WERI and Y79 human retinoblastoma cell lines. Next, the homologous genes in mouse were bisulfite sequenced in the retina and in non-expressing tissues. Finally, bisulfite sequencing was performed on isolated photoreceptor and non-photoreceptor retinal cells isolated by laser capture microdissection. Differential methylation of rhodopsin (RHO), retinal binding protein 3 (RBP3, IRBP) cone opsin, short-wave-sensitive (OPN1SW), cone opsin, middle-wave-sensitive (OPN1MW), and cone opsin, long-wave-sensitive (OPN1LW) was found in the retinoblastoma cell lines that inversely correlated with gene expression levels. Similarly, we found tissue-specific hypomethylation of the promoter region of Rho and Rbp3 in mouse retina as compared to non-expressing tissues, and also observed hypomethylation of retinal-expressed microRNAs. The Rho and Rbp3 promoter regions were unmethylated in expressing photoreceptor cells and methylated in non-expressing, non-photoreceptor cells from the inner nuclear layer. A third regional hypomethylation pattern of photoreceptor-specific genes was seen in a subpopulation of non-expressing photoreceptors (Rho in cones from the Nrl −/− mouse and Opn1sw in rods). These results demonstrate that a number of photoreceptor-specific genes have cell-specific differential DNA methylation that correlates inversely with their expression level. Furthermore, these cell-specific patterns suggest that DNA methylation may play an important role in modulating photoreceptor gene expression in the developing mammalian retina

Age-Related Skeletal Dynamics and Decrease in Bone Strength in DNA Repair Deficient Male Trichothiodystrophy Mice

Accumulation of DNA damage caused by oxidative stress is thought to be one of the main contributors of human tissue aging. Trichothiodystrophy (TTD) mice have a mutation in the Ercc2 DNA repair gene, resulting in accumulation of DNA damage and several features of segmental accelerated aging. We used male TTD mice to study the impact of DNA repair on bone metabolism with age. Analysis of bone parameters, measured by micro-computed tomography, displayed an earlier decrease in trabecular and cortical bone as well as a loss of periosteal apposition and a reduction in bone strength in TTD mice with age compared to wild type mice. Ex vivo analysis of bone marrow differentiation potential showed an accelerated reduction in the number of osteogenic and osteoprogenitor cells with unaltered differentiation capacity. Adipocyte differentiation was normal. Early in life, osteoclast number tended to be increased while at 78 weeks it was significantly lower in TTD mice. Our findings reveal the importance of genome stability and proper DNA repair for skeletal homeostasis with age and support the idea that accumulation of damage interferes with normal skeletal maintenance, causing reduction in the number of osteoblast precursors that are required for normal bone remodeling leading to a loss of bone structure and strength