Assessing the Validity of Sexual Behaviour Reports in a Whole Population Survey in Rural Malawi

Background: Sexual behaviour surveys are widely used, but under-reporting of particular risk behaviours is common, especially by women. Surveys in whole populations provide an unusual opportunity to understand the extent and nature of such under-reporting.Methods: All consenting individuals aged between 15 and 59 within a demographic surveillance site in northern Malawi were interviewed about their sexual behaviour. Validity of responses was assessed by analysis of probing questions; by comparison of results with in-depth interviews and with Herpes simplex type-2 (HSV-2) seropositivity; by comparing reports to same sex and opposite sex interviewers; and by quantifying the partnerships within the local community reported by men and by women, adjusted for response rates.Results: 6,796 women and 5,253 men (83% and 72% of those eligible) consented and took part in sexual behaviour interviews. Probing questions and HSV-2 antibody tests in those who denied sexual activity identified under-reporting for both men and women. Reports varied little by sex or age of the interviewer. The number of marital partnerships reported was comparable for men and women, but men reported about 4 times as many non-marital partnerships. The discrepancy in reporting of non-marital partnerships was most marked for married women (men reported about 7 times as many non-marital partnerships with married women as were reported by married women themselves), but was only apparent in younger married women.Conclusions: We have shown that the under-reporting of non-marital partnerships by women was strongly age-dependent. The extent of under-reporting of sexual activity by young men was surprisingly high. The results emphasise the importance of triangulation, including biomarkers, and the advantages of considering a whole population

Nestedness of Ectoparasite-Vertebrate Host Networks

Determining the structure of ectoparasite-host networks will enable disease ecologists to better understand and predict the spread of vector-borne diseases. If these networks have consistent properties, then studying the structure of well-understood networks could lead to extrapolation of these properties to others, including those that support emerging pathogens. Borrowing a quantitative measure of network structure from studies of mutualistic relationships between plants and their pollinators, we analyzed 29 ectoparasite-vertebrate host networks—including three derived from molecular bloodmeal analysis of mosquito feeding patterns—using measures of nestedness to identify non-random interactions among species. We found significant nestedness in ectoparasite-vertebrate host lists for habitats ranging from tropical rainforests to polar environments. These networks showed non-random patterns of nesting, and did not differ significantly from published estimates of nestedness from mutualistic networks. Mutualistic and antagonistic networks appear to be organized similarly, with generalized ectoparasites interacting with hosts that attract many ectoparasites and more specialized ectoparasites usually interacting with these same “generalized” hosts. This finding has implications for understanding the network dynamics of vector-born pathogens. We suggest that nestedness (rather than random ectoparasite-host associations) can allow rapid transfer of pathogens throughout a network, and expand upon such concepts as the dilution effect, bridge vectors, and host switching in the context of nested ectoparasite-vertebrate host networks

The Genotype Specific Competitive Ability Does Not Correlate with Infection in Natural Daphnia magna Populations

Different evolutionary hypotheses predict a correlation between the fitness of a genotype in the absence of infection and the likelihood to become infected. The cost of resistance hypothesis predicts that resistant genotypes pay a cost of being resistant and are less fit in the absence of parasites. The inbreeding-infection hypothesis predicts that the susceptible individuals are less fit due to inbreeding depression.Here we tested if a host's natural infection status was associated with its fitness. First, we experimentally confirmed that cured but formerly infected Daphnia magna are genetically more susceptible to reinfections with Octosporea bayeri than naturally uninfected D. magna. We then collected from each of 22 populations both uninfected and infected D. magna genotypes. All were treated against parasites and kept in their asexual phase. We estimated their relative fitness in an experiment against a tester genotype and in another experiment in direct competition. Consistently, we found no difference in competitive abilities between uninfected and cured but formerly infected genotypes. This was the case both in the presence as well as in the absence of sympatric parasites during the competition trials.Our data do not support the inbreeding-infection hypothesis. They also do not support a cost of resistance, however ignoring other parasite strains or parasite species. We suggest as a possible explanation for our results that resistance genes might segregate largely independently of other fitness associated genes in this system

Lymph-borne CD8α+ dendritic cells are uniquely able to cross-prime CD8+ T cells with antigen acquired from intestinal epithelial cells

Cross-presentation of cellular antigens is crucial for priming CD8<sup>+</sup> T cells, and generating immunity to intracellular pathogens—particularly viruses. It is unclear which intestinal phagocytes perform this function in vivo. To address this, we examined dendritic cells (DCs) from the intestinal lymph of IFABP-tOVA 232-4 mice, which express ovalbumin in small intestinal epithelial cells (IECs). Among lymph DCs (LDCs) only CD103<sup>+</sup> CD11b<sup>−</sup> CD8α<sup>+</sup> DCs cross-present IEC-derived ovalbumin to CD8<sup>+</sup> OT-I T cells. Similarly, in the mesenteric lymph nodes (MLNs), cross-presentation of IEC–ovalbumin was limited to the CD11c<sup>+</sup> MHCII<sup>hi</sup> CD8α<sup>+</sup> migratory DCs, but absent from all other subsets, including the resident CD8α<sup>hi</sup> DCs. Crucially, delivery of purified CD8α<sup>+</sup> LDCs, but not other LDC subsets, into the MLN subcapsular lymphatic sinus induced proliferation of ovalbumin-specific, gut-tropic CD8<sup>+</sup> T cells <i>in vivo</i>. Finally, in 232-4 mice treated with R848, CD8α<sup>+</sup> LDCs were uniquely able to cross-prime interferon γ-producing CD8<sup>+</sup>T cells and drive their migration to the intestine. Our results clearly demonstrate that migrating CD8α<sup>+</sup> intestinal DCs are indispensable for cross-presentation of cellular antigens and, in conditions of inflammation, for the initial differentiation of effector CD8<sup>+</sup> T cells. They may therefore represent an important target for the development of antiviral vaccinations

Проблемы увеличения продуктивности АПК в Украине и пути повышения его потенциала

Целью статьи является изучение причин снижения показателей продуктивности в агропромышленном комплексе и путей повышения продуктивности сельскохозяйственных культур

Use of MicroRNA Let-7 to Control the Replication Specificity of Oncolytic Adenovirus in Hepatocellular Carcinoma Cells

Highly selective therapy for hepatocellular carcinoma (HCC) remains an unmet medical need. In present study, we found that the tumor suppressor microRNA, let-7 was significantly downregulated in a proportion of primary HCC tissues (12 of 33, 36.4%) and HCC cell lines. In line with this finding, we have engineered a chimeric Ad5/11 fiber oncolytic adenovirus, SG7011let7T, by introducing eight copies of let-7 target sites (let7T) into the 3′ untranslated region of E1A, a key gene associated with adenoviral replication. The results showed that the E1A expression (both RNA and protein levels) of the SG7011let7T was tightly regulated according to the endogenous expression level of the let-7. As contrasted with the wild-type adenovirus and the control virus, the replication of SG7011let7T was distinctly inhibited in normal liver cells lines (i.e. L-02 and WRL-68) expressing high level of let-7 (>300 folds), whereas was almost not impaired in HCC cells (i.e. Hep3B and PLC/PRF/5) with low level of let-7. Consequently, the cytotoxicity of SG7011let7T to normal liver cells was successfully decreased while was almost not attenuated in HCC cells in vitro. The antitumor ability of SG7011let7T in vivo was maintained in mice with Hep3B xenograft tumor, whereas was greatly decreased against the SMMC-7721 xenograft tumor expressing a high level of let-7 similar with L-02 when compared to the wild-type adenovirus. These results suggested that SG7011let7T may be a promising anticancer agent or vector to mediate the expression of therapeutic gene, broadly applicable in the treatment for HCC and other cancers where the let-7 gene is downregulated

Disrupted lymph node and splenic stroma in mice with induced inflammatory melanomas is associated with impaired recruitment of T and dendritic cells

International audienceMigration of dendritic cells (DC) from the tumor environment to the T cell cortex in tumor-draining lymph nodes (TDLN) is essential for priming naïve T lymphocytes (TL) to tumor antigen (Ag). We used a mouse model of induced melanoma in which similar oncogenic events generate two phenotypically distinct melanomas to study the influence of tumor-associated inflammation on secondary lymphoid organ (SLO) organization. One tumor promotes inflammatory cytokines, leading to mobilization of immature myeloid cells (iMC) to the tumor and SLO; the other does not. We report that inflammatory tumors induced alterations of the stromal cell network of SLO, profoundly altering the distribution of TL and the capacity of skin-derived DC and TL to migrate or home to TDLN. These defects, which did not require tumor invasion, correlated with loss of fibroblastic reticular cells in T cell zones and in impaired production of CCL21. Infiltrating iMC accumulated in the TDLN medulla and the splenic red pulp. We propose that impaired function of the stromal cell network during chronic inflammation induced by some tumors renders spleens non-receptive to TL and TDLN non-receptive to TL and migratory DC, while the entry of iMC into these perturbed SLO is enhanced. This could constitute a mechanism by which inflammatory tumors escape immune control. If our results apply to inflammatory tumors in general, the demonstration that SLO are poorly receptive to CCR7-dependent migration of skin-derived DC and naïve TL may constitute an obstacle for proposed vaccination or adoptive TL therapies of their hosts

γδ T Cells Are Reduced and Rendered Unresponsive by Hyperglycemia and Chronic TNFα in Mouse Models of Obesity and Metabolic Disease

Epithelial cells provide an initial line of defense against damage and pathogens in barrier tissues such as the skin; however this balance is disrupted in obesity and metabolic disease. Skin γδ T cells recognize epithelial damage, and release cytokines and growth factors that facilitate wound repair. We report here that hyperglycemia results in impaired skin γδ T cell proliferation due to altered STAT5 signaling, ultimately resulting in half the number of γδ T cells populating the epidermis. Skin γδ T cells that overcome this hyperglycemic state are unresponsive to epithelial cell damage due to chronic inflammatory mediators, including TNFα. Cytokine and growth factor production at the site of tissue damage was partially restored by administering neutralizing TNFα antibodies in vivo. Thus, metabolic disease negatively impacts homeostasis and functionality of skin γδ T cells, rendering host defense mechanisms vulnerable to injury and infection

Migratory Dermal Dendritic Cells Act as Rapid Sensors of Protozoan Parasites

Dendritic cells (DC), including those of the skin, act as sentinels for intruding microorganisms. In the epidermis, DC (termed Langerhans cells, LC) are sessile and screen their microenvironment through occasional movements of their dendrites. The spatio-temporal orchestration of antigen encounter by dermal DC (DDC) is not known. Since these cells are thought to be instrumental in the initiation of immune responses during infection, we investigated their behavior directly within their natural microenvironment using intravital two-photon microscopy. Surprisingly, we found that, under homeostatic conditions, DDC were highly motile, continuously crawling through the interstitial space in a Gαi protein-coupled receptor–dependent manner. However, within minutes after intradermal delivery of the protozoan parasite Leishmania major, DDC became immobile and incorporated multiple parasites into cytosolic vacuoles. Parasite uptake occurred through the extension of long, highly dynamic pseudopods capable of tracking and engulfing parasites. This was then followed by rapid dendrite retraction towards the cell body. DDC were proficient at discriminating between parasites and inert particles, and parasite uptake was independent of the presence of neutrophils. Together, our study has visualized the dynamics and microenvironmental context of parasite encounter by an innate immune cell subset during the initiation of the immune response. Our results uncover a unique migratory tissue surveillance program of DDC that ensures the rapid detection of pathogens