Antifungal immune responses in mosquitoes (Diptera: Culicidae): A review.

Mosquitoes transmit many parasites and pathogens to humans that cause significant morbidity and mortality. As such, we are constantly looking for new methods to reduce mosquito populations, including the use of effective biological controls. Entomopathogenic fungi are excellent candidate biocontrol agents to control mosquitoes. Understanding the complex ecological, environmental, and molecular interactions between hosts and pathogens are essential to create novel, effective and safe biocontrol agents. Understanding how mosquitoes recognize and eliminate pathogens such as entomopathogenic fungi may allow us to create insect-order specific biocontrol agents to reduce pest populations. Here we summarize the current knowledge of fungal infection, colonization, development, and replication within mosquitoes and the innate immune responses of the mosquitoes towards the fungal pathogens, emphasizing those features required for an effective mosquito biocontrol agent.

The Role of Bacterial Symbionts in Triatomines: An Evolutionary Perspective.

Insects have established mutualistic symbiotic interactions with microorganisms that are beneficial to both host and symbiont. Many insects have exploited these symbioses to diversify and expand their ecological ranges. In the Hemiptera (i.e., aphids, cicadas, and true bugs), symbioses have established and evolved with obligatory essential microorganisms (primary symbionts) and with facultative beneficial symbionts (secondary symbionts). Primary symbionts are usually intracellular microorganisms found in insects with specialized diets such as obligate hematophagy or phytophagy. Most Heteroptera (true bugs), however, have gastrointestinal (GI) tract extracellular symbionts with functions analogous to primary endosymbionts. The triatomines, are vectors of the human parasite, Trypanosoma cruzi. A description of their small GI tract microbiota richness was based on a few culturable microorganisms first described almost a century ago. A growing literature describes more complex interactions between triatomines and bacteria with properties characteristic of both primary and secondary symbionts. In this review, we provide an evolutionary perspective of beneficial symbioses in the Hemiptera, illustrating the context that may drive the evolution of symbioses in triatomines. We highlight the diversity of the triatomine microbiota, bacterial taxa with potential to be beneficial symbionts, the unique characteristics of triatomine-bacteria symbioses, and the interactions among trypanosomes, microbiota, and triatomines.

Scavenger Receptor Cysteine-Rich domains of Lysyl Oxidase-Like2 regulate endothelial ECM and angiogenesis through non-catalytic scaffolding mechanisms.

Lysyl oxidases are major actors of microenvironment and extracellular matrix (ECM) remodeling. These cross-linking enzymes are thus involved in many aspects of physiopathology, including tumor progression, fibrosis and cardiovascular diseases. We have already shown that Lysyl Oxidase-Like 2 (LOXL2) regulates collagen IV deposition by endothelial cells and angiogenesis. We here provide evidence that LOXL2 also affects deposition of other ECM components, including fibronectin, thus altering structural and mechanical properties of the matrix generated by endothelial cells. LOXL2 interacts intracellularly and directly with collagen IV and fibronectin before incorporation into ECM fibrillar structures upon exocytosis, as demonstrated by TIRF time-lapse microscopy. Furthermore, surface plasmon resonance experiments using recombinant scavenger receptor cysteine-rich (SRCR) domains truncated for the catalytic domain demonstrated their direct binding to collagen IV. We thus used directed mutagenesis to investigate the role of LOXL2 catalytic domain. Neither enzyme activity nor catalytic domain were necessary for collagen IV deposition and angiogenesis, whereas the SRCR domains were effective for these processes. Finally, surface coating with recombinant SRCR domains restored deposition of collagen IV by LOXL2-depleted cells. We thus propose that LOXL2 SRCR domains orchestrate scaffolding of the vascular basement membrane and angiogenesis through interactions with collagen IV and fibronectin, independently of the enzymatic cross-linking activity.

TIM-1 Ubiquitination Mediates Dengue Virus Entry.

Dengue virus (DENV) is a major human pathogen causing millions of infections yearly. Despite intensive investigations, a DENV receptor that directly participates in virus internalization has not yet been characterized. Here, we report that the phosphatidylserine receptor TIM-1 is an authentic DENV entry receptor that plays an active role in virus endocytosis. Genetic ablation of TIM-1 strongly impaired DENV infection. Total internal reflection fluorescence microscopy analyses of live infected cells show that TIM-1 is mostly confined in clathrin-coated pits and is co-internalized with DENV during viral entry. TIM-1 is ubiquitinated at two lysine residues of its cytoplasmic domain, and this modification is required for DENV endocytosis. Furthermore, STAM-1, a component of the ESCRT-0 complex involved in intracellular trafficking of ubiquitinated cargos, interacts with TIM-1 and is required for DENV infection. Overall, our results show that TIM-1 is the first bona fide receptor identified for DENV.

A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors.

Dengue virus (DENV) infections cause the most prevalent mosquito-borne viral disease worldwide, for which no therapies are available. DENV encodes seven non-structural (NS) proteins that co-assemble and recruit poorly characterized host factors to form the DENV replication complex essential for viral infection. Here, we provide a global proteomic analysis of the human host factors that interact with the DENV NS1 protein. Combined with a functional RNAi screen, this study reveals a comprehensive network of host cellular processes involved in DENV infection and identifies DENV host restriction and dependency factors. We highlight an important role of RACK1 and the chaperonin TRiC (CCT) and oligosaccharyltransferase (OST) complexes during DENV replication. We further show that the OST complex mediates NS1 and NS4B glycosylation, and pharmacological inhibition of its N-glycosylation function strongly impairs DENV infection. In conclusion, our study provides a global interactome of the DENV NS1 and identifies host factors targetable for antiviral therapies.

A soft cortex is essential for asymmetric spindle positioning in mouse oocytes.

At mitosis onset, cortical tension increases and cells round up, ensuring correct spindle morphogenesis and orientation. Thus, cortical tension sets up the geometric requirements of cell division. On the contrary, cortical tension decreases during meiotic divisions in mouse oocytes, a puzzling observation because oocytes are round cells, stable in shape, that actively position their spindles. We investigated the pathway leading to reduction in cortical tension and its significance for spindle positioning. We document a previously uncharacterized Arp2/3-dependent thickening of the cortical F-actin essential for first meiotic spindle migration to the cortex. Using micropipette aspiration, we show that cortical tension decreases during meiosis I, resulting from myosin-II exclusion from the cortex, and that cortical F-actin thickening promotes cortical plasticity. These events soften and relax the cortex. They are triggered by the Mos-MAPK pathway and coordinated temporally. Artificial cortex stiffening and theoretical modelling demonstrate that a soft cortex is essential for meiotic spindle positioning.