Differential impact of LPG-and PG-deficient Leishmania major mutants on the immune response of human dendritic cells

<div><p>Background</p><p><i>Leishmania major</i> infection induces robust interleukin-12 (IL12) production in human dendritic cells (hDC), ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of <i>Leishmania</i> parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG) and other phosphoglycan-containing molecules (PGs), making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS) responsible for IL12 induction.</p><p>Methodology/Principal Findings</p><p>Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating <i>L</i>. <i>major</i> Friedlin V1 mutants defective in LPG alone, (FV1 <i>lpg1-</i>), or generally deficient for all PGs, (FV1 <i>lpg2-</i>). Infection with metacyclic, infective stage, <i>L</i>. <i>major</i> or purified LPG induced high levels of <i>IL12B</i> subunit gene transcripts in hDCs, which was abrogated with FV1 <i>lpg1-</i> infections. In contrast, hDC infections with FV1 <i>lpg2-</i> displayed increased <i>IL12B</i> expression, suggesting other PG-related/<i>LPG2</i> dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 <i>lpg1-</i>, FV1 <i>lpg2-</i> infections revealed that FV1 <i>lpg1-</i> mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB) and Interferon Regulatory Factor (IRF) mediated transcription.</p><p>Conclusions/Significance</p><p>These data suggest that <i>L</i>. <i>major</i> LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring <i>Leishmania</i> surface glycoconjugates that result in modulation of host cellular IL12.</p></div

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

Deployment of a wireless sensor network for aquaculture and lake resource management

We describe the ongoing deployment of a wireless network system for monitoring aquaculture applications and managing a lake resource in one of the Seven Lakes in San Pablo, Laguna, Philippines. Field servers are deployed to measure water quality parameters such as dissolved oxygen and temperature. In addition, a novel floating platform field server is developed to gather data in the middle parts of the lake. Cameras are also deployed to monitor different aspects of the area. A knowledge management system allows dissemination of these data and other information that would be of interest to stakeholders and the local community

Current Therapeutic Strategies in Diabetic Foot Ulcers

Diabetic foot ulcers (DFUs) are the fastest growing chronic complication of diabetes mellitus, with more than 400 million people diagnosed globally, and the condition is responsible for lower extremity amputation in 85% of people affected, leading to high-cost hospital care and increased mortality risk. Neuropathy and peripheral arterial disease trigger deformities or trauma, and aggravating factors such as infection and edema are the etiological factors for the development of DFUs. DFUs require identifying the etiology and assessing the co-morbidities to provide the correct therapeutic approach, essential to reducing lower-extremity amputation risk. This review focuses on the current treatment strategies for DFUs with a special emphasis on tissue engineering techniques and regenerative medicine that collectively target all components of chronic wound pathology

Chemical diversity and potential biological functions of the pygidial gland secretions in two species of Neotropical dung roller beetles

Dung roller beetles of the genus Canthon (Coleoptera: Scarabaeinae) emit an odorous secretion from a pair of pygidial glands. To investigate the chemical composition of these secretions, we used stir bar sorptive extraction (SBSE), coupled with gas chromatography–mass spectrometry (GC–MS) for analysis of extracts of pygidial gland secretions secreted by the dung roller beetles Canthon femoralis femoralis and Canthon cyanellus cyanellus. Chemical analyses of volatiles collected from pygidial gland secretions comprise a great diversity of the functional groups. Chemical profile comparisons showed high intra- and interspecific variability. The pygidial gland secretion of Canthon f. femoralis was dominated by sesquiterpene hydrocarbons, whereas the profile of Canthon c. cyanellus was dominated by carboxylic acids. The different pygidial secretions have a high diversity of chemical compounds suggesting a multifunctional nature involving some key functions in the biology. We discuss the biological potential of these compounds found in the pygidial glands of each species with respect to their ecological and behavioral relevance.We are grateful to CONACYT Mexico for awarding a doctoral scholarship (14643) and a postdoctoral fellowship (184878 and 203310) to V.C.G. This paper is partly based on the Ph.D. thesis of V.C.G. This work was supported by CONACYT Mexico (168373-Etapa II) and the Ministerio de Ciencia e Innovación (Spain) (CGL2008-03878)