Disentangling social, environmental, and zoonotic transmission pathways of a gastrointestinal protozoan (Blastocystis spp.) in northeast Madagascar.

OBJECTIVES: Understanding disease transmission is a fundamental challenge in ecology. We used transmission potential networks to investigate whether a gastrointestinal protozoan (Blastocystis spp.) is spread through social, environmental, and/or zoonotic pathways in rural northeast Madagascar. MATERIALS AND METHODS: We obtained survey data, household GPS coordinates, and fecal samples from 804 participants. Surveys inquired about social contacts, agricultural activity, and sociodemographic characteristics. Fecal samples were screened for Blastocystis using DNA metabarcoding. We also tested 133 domesticated animals for Blastocystis. We used network autocorrelation models and permutation tests (network k-test) to determine whether networks reflecting different transmission pathways predicted infection. RESULTS: We identified six distinct Blastocystis subtypes among study participants and their domesticated animals. Among the 804 human participants, 74% (n = 598) were positive for at least one Blastocystis subtype. Close proximity to infected households was the most informative predictor of infection with any subtype (model averaged OR [95% CI]: 1.56 [1.33-1.82]), and spending free time with infected participants was not an informative predictor of infection (model averaged OR [95% CI]: 0.95 [0.82-1.10]). No human participant was infected with the same subtype as the domesticated animals they owned. DISCUSSION: Our findings suggest that Blastocystis is most likely spread through environmental pathways within villages, rather than through social or animal contact. The most likely mechanisms involve fecal contamination of the environment by infected individuals or shared food and water sources. These findings shed new light on human-pathogen ecology and mechanisms for reducing disease transmission in rural, low-income settings.

Pyrethroid susceptibility reversal in Aedes aegypti: A longitudinal study in Tapachula, Mexico.

Pyrethroid resistance in Aedes aegypti has become widespread after almost two decades of frequent applications to reduce the transmission of mosquito-borne diseases. Because few insecticide classes are available for public health use, insecticide resistance management (IRM) is proposed as a strategy to retain their use. A key hypothesis of IRM assumes that negative fitness is associated with resistance, and when insecticides are removed from use, susceptibility is restored. In Tapachula, Mexico, pyrethroids (PYRs) were used exclusively by dengue control programs for 15 years, thereby contributing to selection for high PYR resistance in mosquitoes and failure in dengue control. In 2013, PYRs were replaced by organophosphates-insecticides from a class with a different mode of action. To test the hypothesis that PYR resistance is reversed in the absence of PYRs, we monitored Ae. aegypti's PYR resistance from 2016 to 2021 in Tapachula. We observed significant declining rates in the lethal concentration 50 (LC50), for permethrin and deltamethrin. For each month following the discontinuation of PYR use by vector control programs, we observed increases in the odds of mosquitoes dying by 1.5% and 8.4% for permethrin and deltamethrin, respectively. Also, knockdown-resistance mutations (kdr) in the voltage-gated sodium channel explained the variation in the permethrin LC50s, whereas variation in the deltamethrin LC50s was only explained by time. This trend was rapidly offset by application of a mixture of neonicotinoid and PYRs by vector control programs. Our results suggest that IRM strategies can be used to reverse PYR resistance in Ae. aegypti; however, long-term commitment by operational and community programs will be required for success.

Evaluation of commercial aerosol insecticides for control of Aedes aegypti susceptible or resistant to pyrethroids.

OBJECTIVE: To evaluate indoor use of commercial aerosols for dengue vector mosquito control, and estimate the number of treatable houses per can. MATERIALS AND METHODS: Four aerosol products containing combinations of pyrethroids (two containing propoxur and one containing synergists too), were evaluated with mosquitoes in a room of a Tapachulastyle house. Eight cages containing 20 insecticide susceptible or resistant females were hung from tripods, another set was placed in sheltered areas of the room. From the entrance of the room, one of 4-9 concentrations was sprayed for each aerosol, leaving the mosquitoes for 30 min after sprayed. Mortality was recorded after 24 h and lethal concentrations were calculated. RESULTS: Aerosol A had the highest LC50, with 0.308 g for mosquitoes hanging from tripods and 0.453 g for sheltered mosquitoes; followed by aerosols C, D and B, with statistical differences between types of exposure. CONCLUSIONS: Aerosols B-D could spray 20-25 3-room houses (56 m3-room), killing all resistant mosquitoes. Aerosols may become a good tool for indoor mosquito control, if the optimal concentration and correct spray method are used.

Getting it right: Teaching undergraduate biology to undermine racial essentialism.

How we teach human genetics matters for social equity. The biology curriculum appears to be a crucial locus of intervention for either reinforcing or undermining students' racial essentialist views. The Mendelian genetic models dominating textbooks, particularly in combination with racially inflected language sometimes used when teaching about monogenic disorders, can increase middle and high school students' racial essentialism and opposition to policies to increase equity. These findings are of particular concern given the increasing spread of racist misinformation online and the misappropriation of human genomics research by white supremacists, who take advantage of low levels of genetics literacy in the general public. Encouragingly, however, teaching updated information about the geographical distribution of human genetic variation and the complex, multifactorial basis of most human traits, reduces students' endorsement of racial essentialism. The genetics curriculum is therefore a key tool in combating misinformation and scientific racism. Here, we describe a framework and example teaching materials for teaching students key concepts in genetics, human evolutionary history, and human phenotypic variation at the undergraduate level. This framework can be flexibly applied in biology and anthropology classes and adjusted based on time availability. Our goal is to provide undergraduate-level instructors with varying levels of expertise with a set of evidence-informed tools for teaching human genetics to combat scientific racism, including an evolving set of instructional resources, as well as learning goals and pedagogical approaches. Resources can be found at https://noto.li/YIlhZ5. Additionally, we hope to generate conversation about integrating modern genetics into the undergraduate curriculum, in light of recent findings about the risks and opportunities associated with teaching genetics.

Aedes aegypti, Ae. albopictus and Culex quinquefasciatus Adults Found Coexisting in Urban and Semiurban Dwellings of Southern Chiapas, Mexico.

Tapachula, Mexico, a tropical city, is an endemic area for dengue, in addition to several outbreaks in the last decade with chikungunya and zika. As part of the migratory corridor from Central to North America and the risks of scattered infectious diseases that this implies, the identification and distribution of potential disease vectors in and around residential areas are essential in terms of entomological surveillance for the prevention of disease outbreaks. The identification of mosquito species of medical importance coexisting in houses and cemeteries in Tapachula and two semiurban sites in southern Chiapas was investigated. Adult mosquitoes were collected from May to December 2018, resting inside and outside houses and in the tombstones and fallen tree leaves in cemeteries. A total of 10,883 mosquitoes belonging to three vector species were collected across 20 sites; 6738 were from neighborhood houses, of which 55.4% were Culex quinquefasciatus, 41.6% Aedes aegypti, and 2.9% Ae. albopictus. Aedes aegypti was the most common mosquito resting inside houses (56.7%), while Ae. albopictus and Cx. quinquefasciatus were mostly found resting outside houses (75.7%). In the cemeteries, Cx. quinquefasciatus (60.8%) and Ae. albopictus (37.3%) were the most abundant, while Ae. aegypti (1.9%) was the least abundant. This is the first report to identify adults of three major disease vector species coexisting in the domestic environment of urban and semiurban sites and Ae. albopictus adult resting inside of urban houses in Mexico. It would be opportune to consider comprehensive strategies that can be applied in this region to control the three species at the same time and avoid outbreaks of the diseases they transmit.

Minimalist revision of Mesochorus Gravenhorst, 1829 (Hymenoptera: Ichneumonidae: Mesochorinae) from Área de Conservación Guanacaste, Costa Rica, with 158 new species and host records for 129 species / Revisión minimalista de Mesochorus Gravenhorst, 1829 (Hymenoptera: Ichneumonidae: Mesochorinae) del Área de Conservación Guanacaste, Costa Rica, con 158 especies nuevas y registros de hospedantes para 129 especies

Introduction: Species of Mesochorus are found worldwide and members of this genus are primarily hyperparasitoids of Ichneumonoidea and Tachinidae. Objectives: To describe species of Costa Rican Mesochorus reared from caterpillars and to a lesser extent Malaise-trapped. Methods: The species are diagnosed by COI mtDNA barcodes, morphological inspection, and host data. A suite of images and host data (plant, caterpillar, and primary parasitoid) are provided for each species. Results: A total of 158 new species of Mesochorus. Sharkey is the taxonomic authority for all. Conclusions: This demonstrates a practical application of DNA barcoding that can be applied to the masses of undescribed neotropical insect species in hyperdiverse groups.

Introducción: Las especies de Mesochorus se encuentran en todo el mundo y los miembros de este género son principalmente hiperparasitoides de las familias Ichneumonoidea y Tachinidae. Objetivos: Describir las especies de Mesochorus costarricenses obtenidas de orugas y en menor medida por trampas Malaise. Métodos: Las especies se diagnosticaron mediante el uso de código de barra molecular por COI del ADNmt, inspección morfológica y datos del huésped. Se proporciona un conjunto de imágenes y datos de los huéspedes (planta, oruga y parasitoide primario) para cada especie. Resultados: Se encontró un total de 158 nuevas especies de Mesochorus. Sharkey es la autoridad taxonómica para todas las especies. Conclusiones: Se demuestra una aplicación práctica del código de barras de ADN que se puede aplicar a grandes cantidades de especies de insectos neotropicales no descritas para grupos hiperdiversos.

Resistance to Pyrethroids in the Malaria Vector Anopheles albimanus in Two Important Villages in the Soconusco Region of Chiapas, Mexico, 2022.

Chiapas State comprises the largest malaria foci from Mexico, and 57% of the autochthonous cases in 2021, all with Plasmodium vivax infections, were reported in this State. Southern Chiapas is at constant risk of cases imported due to migratory human flow. Since chemical control of vector mosquitoes is the main entomological action implemented for the prevention and control of vector-borne diseases, this work aimed to investigate the susceptibility of Anopheles albimanus to insecticides. To this end, mosquitoes were collected in cattle in two villages in southern Chiapas in July-August 2022. Two methods were used to evaluate the susceptibility: the WHO tube bioassay and the CDC bottle bioassay. For the latter, diagnostic concentrations were calculated. The enzymatic resistance mechanisms were also analyzed. CDC diagnostic concentrations were obtained; 0.7 µg/mL deltamethrin, 12 µg/mL permethrin, 14.4 µg/mL malathion, and 2 µg/mL chlorpyrifos. Mosquitoes from Cosalapa and La Victoria were susceptible to organophosphates and to bendiocarb, but resistant to pyrethroids, with mortalities between 89% and 70% (WHO), and 88% and 78% (CDC), for deltamethrin and permethrin, respectively. High esterase levels are suggested as the resistance mechanism involved in the metabolism of pyrethroids in mosquitoes from both villages. Mosquitoes from La Victoria might also involve cytochrome P450. Therefore, organophosphates and carbamates are suggested to currently control An. albimanus. Its use might reduce the frequency of resistance genes to pyrethroids and vector abundance and may impede the transmission of malaria parasites.

Current enzyme-mediated insecticide resistance status of Aedes aegypti populations from a dengue-endemic city in southern Mexico.

OBJECTIVE: To identify the enzyme-mediated insecticide resistance in Aedes aegypti in Tapachula, Mexico. MATERIALS AND METHODS: Biochemical assays were undertaken to determine the enzyme levels in mosquitoes from 22 sites collected in 2018 and 2020 in Tapachula. Results of 2018 were correlated with the resistance to insecticides pub-lished. RESULTS: Mosquitoes had higher levels than those of the susceptible strain in 2018 and 2020 respectively of α-esterases in 15 and 12 sites; ß-esterases in 7 and 6 sites; glutathione-S-transferases in 11 and 19 sites; ρNPA-esterases in 21 and 17 sites; and cytochromes P450 in 20 and 22 sites. In mosquitoes of 2018, there was a moderate correlation between previously documented Malathion resistance ratios and the insensitive acetylcholinesterase (r=0.459, p= 0.03). CONCLUSIONS: The elevated enzyme levels found indicate its contribution to the resistance to pyrethroids and organo-phosphates already published in mosquitoes from Tapachula. Bioassays using enzyme inhibitors resulted in greater mor-tality, confirming that metabolism contributes to resistance.

Comparing transmission potential networks based on social network surveys, close contacts and environmental overlap in rural Madagascar.

Social and spatial network analysis is an important approach for investigating infectious disease transmission, especially for pathogens transmitted directly between individuals or via environmental reservoirs. Given the diversity of ways to construct networks, however, it remains unclear how well networks constructed from different data types effectively capture transmission potential. We used empirical networks from a population in rural Madagascar to compare social network survey and spatial data-based networks of the same individuals. Close contact and environmental pathogen transmission pathways were modelled with the spatial data. We found that naming social partners during the surveys predicted higher close-contact rates and the proportion of environmental overlap on the spatial data-based networks. The spatial networks captured many strong and weak connections that were missed using social network surveys alone. Across networks, we found weak correlations among centrality measures (a proxy for superspreading potential). We conclude that social network surveys provide important scaffolding for understanding disease transmission pathways but miss contact-specific heterogeneities revealed by spatial data. Our analyses also highlight that the superspreading potential of individuals may vary across transmission modes. We provide detailed methods to construct networks for close-contact transmission pathogens when not all individuals simultaneously wear GPS trackers.

Insecticide resistance in Aedes aegypti from Tapachula, Mexico: Spatial variation and response to historical insecticide use.

BACKGROUND: Insecticide use continues as the main strategy to control Aedes aegypti, the vector of dengue, Zika, chikungunya, and yellow fever. In the city of Tapachula, Mexico, mosquito control programs switched from pyrethroids to organophosphates for outdoor spatial spraying in 2013. Additionally, the spraying scheme switched from total coverage to focused control, prioritizing areas with higher entomological-virological risk. Five years after this strategy had been implemented, we evaluated the status and variability of insecticide resistance among Ae. aegypti collected at 26 sites in Tapachula. METHODOLOGY/PRINCIPAL FINDINGS: We determined the lethal concentrations at 50% of the tested populations (LC50) using a bottle bioassay, and then, we calculated the resistance ratio (RR) relative to the susceptible New Orleans strain. Permethrin and deltamethrin (pyrethroids), chlorpyrifos and malathion (organophosphates), and bendiocarb (carbamate) were tested. The frequencies of the substitutions V1016I and F1534C, which are in the voltage-gated sodium channel and confer knockdown-resistance (kdr) to pyrethroid insecticides, were calculated. Despite 5 years having passed since the removal of pyrethroids from the control programs, Ae. aegypti remained highly resistant to permethrin and deltamethrin (RR > 10-fold). In addition, following 5 years of chlorpyrifos use, mosquitoes at 15 of 26 sites showed moderate resistance to chlorpyrifos (5- to 10-fold), and the mosquitoes from one site were highly resistant. All sites had low resistance to malathion (< 5-fold). Resistance to bendiocarb was low at 19 sites, moderate at five, and high at two. Frequencies of the V1016I ranged from 0.16-0.71, while C1534 approached fixation at 23 sites (0.8-1). Resistance profiles and kdr allele frequencies varied across Tapachula. The variability was not associated with a spatial pattern at the scale of the sampling. CONCLUSION/SIGNIFICANCE: Mosquito populations respond to selection pressure at a focal scale in the field. Spatial variation across sites highlights the importance of testing multiple sites within geographical regions.

Permethrin resistance in Aedes aegypti: Genomic variants that confer knockdown resistance, recovery, and death.

Pyrethroids are one of the few classes of insecticides available to control Aedes aegypti, the major vector of dengue, chikungunya, and Zika viruses. Unfortunately, evolving mechanisms of pyrethroid resistance in mosquito populations threaten our ability to control disease outbreaks. Two common pyrethroid resistance mechanisms occur in Ae. aegypti: 1) knockdown resistance, which involves amino acid substitutions at the pyrethroid target site-the voltage-gated sodium channel (VGSC)-and 2) enhanced metabolism by detoxification enzymes. When a heterogeneous population of mosquitoes is exposed to pyrethroids, different responses occur. During exposure, a proportion of mosquitoes exhibit immediate knockdown, whereas others are not knocked-down and are designated knockdown resistant (kdr). When these individuals are removed from the source of insecticide, the knocked-down mosquitoes can either remain in this status and lead to dead or recover within a few hours. The proportion of these phenotypic responses is dependent on the pyrethroid concentration and the genetic background of the population tested. In this study, we sequenced and performed pairwise genome comparisons between kdr, recovered, and dead phenotypes in a pyrethroid-resistant colony from Tapachula, Mexico. We identified single-nucleotide polymorphisms (SNPs) associated with each phenotype and identified genes that are likely associated with the mechanisms of pyrethroid resistance, including detoxification, the cuticle, and insecticide target sites. We identified high association between kdr and mutations at VGSC and moderate association with additional insecticide target site, detoxification, and cuticle protein coding genes. Recovery was associated with cuticle proteins, the voltage-dependent calcium channel, and a different group of detoxification genes. We provide a list of detoxification genes under directional selection in this field-resistant population. Their functional roles in pyrethroid metabolism and their potential uses as genomic markers of resistance require validation.

One health disparities and COVID-19.

The global impact of the COVID-19 pandemic has disproportionately affected some communities and populations more than others. We propose that an interdisciplinary framework of 'One Health Disparities' advances understanding of the social and systemic issues that drive COVID-19 in vulnerable populations. One Health Disparities integrates the social environment with One Health perspectives on the interconnectedness of human, animal, and environmental health. To apply this framework, we consider One Health Disparities that emerge in three key components of disease transmission: exposure, susceptibility, and disease expression. Exposure disparities arise through variation in contact with COVID-19's causative agent, SARS-CoV-2. Disparities in susceptibility and disease expression also exist; these are driven by biological and social factors, such as diabetes and obesity, and through variation in access to healthcare. We close by considering how One Health Disparities informs understanding of spillback into new animal reservoirs, and what this might mean for further human health disparities. LAY SUMMARY: One Health focuses on interconnections between human, animal, and environmental health. We propose that social environments are also important to One Health and help illuminate disparities in the coronavirus pandemic, including its origins, transmission and susceptibility among humans, and spillback to other species. We call this framework One Health Disparities.

Permethrin Resistance Status and Associated Mechanisms in Aedes albopictus (Diptera: Culicidae) From Chiapas, Mexico.

There are major public health concerns regarding the spread of mosquito-borne diseases such as dengue, Zika, and chikungunya, which are mainly controlled by using insecticides against the vectors, Aedes aegypti (Linnaeus) and Aedes albopictus (Skuse). Pyrethroids are the primary class of insecticides used for vector control, due to their rapid knockdown effect and low toxicity to vertebrates. Unfortunately, continued use of pyrethroids has led to widespread insecticide resistance in Ae. aegypti; however, we lack information for Ae. albopictus-a sympatric species in Chiapas since 2002. In this study, we evaluated the permethrin resistance status of Ae. albopictus collected from Mexico and Texas. We also selected for permethrin resistance in the laboratory and investigated the potential mechanisms conferring resistance in this species. Knockdown resistance mutations, specifically F1534C, in the voltage-gated sodium channel gene, and increased activity of detoxifying enzymes were evaluated. Low levels of permethrin resistance (<2.4-fold) were observed in our field populations of Ae. albopictus and the F1534C mutation was not detected in any of the sites. Low levels of resistance were also observed in the artificially selected strain. There was significantly higher cytochrome P450 activity in our permethrin-selected and nonselected strains from Mexico compared to the control strain. Our results suggest the Ae. albopictus sampled from 2016 are mostly susceptible to pyrethroids. These results contrast with the high levels of permethrin resistance (>58-fold) found in Ae. aegypti from the same sites in Mexico. This research indicates the importance of continued monitoring of Ae. albopictus populations to prevent resistance from developing in the future.

Resistencia a insecticidas en Aedes aegypti y Aedes albopictus (Diptera: Culicidae) de Tapachula, Chiapas, México / Insecticide resistance in Aedes aegypti and Ae. albopictus (Diptera: Culicidae) populations from Tapachula, Chiapas, Mexico

Resumen: Objetivo: Determinar la resistencia a insecticidas en Ae. aegypti y Ae. albopictus de Tapachula, Chiapas, México. Material y métodos: Se utilizaron ovitrampas para obtener huevos de mosquitos Aedes y se realizaron pruebas de susceptibilidad (CDC) y ensayos enzimáticos con la primera generación. Resultados: Aedes aegypti mostró resistencia a deltametrina, permetrina, malatión, clorpirifos, temefos y a bendiocarb (CARB), mientras que Aedes albopictus a malatión y en menor grado a cloripirifos, temefos, permetrina y deltametrina. Ambas especies mostraron altos niveles de enzimas como citocomo P450 y glutatión S-tranferasa, mientras que los niveles de esterasas variaron por especie y sitio muestreado. Se detectó acetilcolinesterasa insensible a insecticidas en ambas especies. Conclusión: En un hábitat urbano de Tapachula, Chiapas, México donde se aplica control con insecticidas Ae. aegypti y Ae. albopictus sólo son susceptibles al propoxur.

Abstract: Objective: To determine the insecticide resistance status of Ae. aegypti and Ae. albopictus from Tapachula, México. Materials and methods: Mosquito eggs were collected with the use of ovitraps and CDC susceptibility bioassays and biochemical assays were conducted to determine resistance levels and resistance mechanisms, respectively. Results: Ae. aegypti showed resistance to deltamethrin and permethrin (PYRs), malathion, chlorpyrifos and temephos (OP), and to bendiocarb (CARB), while Ae. albopictus showed resistance to malathion and to a lesser intensity to chlorypirifos, temephos, permethrin and deltamethrin. Both species showed high levels of P450 and GSTs, while levels of esterases varied by species and collection site. Altered acethilcholinesterase was detected in both species. Conclusion: In an urban habitat from Tapachula, Chiapas, Mexico where vector control using insecticides takes place, Ae. aegypti and Ae. albopictus are only susceptible to propoxur.

[Insecticide resistance in Aedes aegypti and Ae. albopictus (Diptera: Culicidae) populations from Tapachula, Chiapas, Mexico]. / Resistencia a insecticidas en Aedes aegypti y Aedes albopictus (Diptera: Culicidae) de Tapachula, Chiapas, México.

OBJECTIVE: To determine the insecticide resistance status of Ae. aegypti and Ae. albopictus from Tapachula, México. MATERIALS AND METHODS: Mosquito eggs were collected with the use of ovitraps and CDC susceptibility bioassays and biochemical assays were conducted to determine resistance levels and resistance mechanisms, respectively. RESULTS: Ae. aegypti showed resistance to deltamethrin and permethrin (PYRs), malathion, chlorpyrifos and temephos (OP), and to bendiocarb (CARB), while Ae. albopictus showed resistance to malathion and to a lesser intensity to chlorypirifos, temephos, permethrin and deltamethrin. Both species showed high levels of P450 and GSTs, while levels of esterases varied by species and collection site. Altered acethilcholinesterase was detected in both species. CONCLUSIONS: In an urban habitat from Tapachula, Chiapas, Mexico where vector control using insecticides takes place, Ae. aegypti and Ae. albopictus are only susceptible to propoxur.

OBJETIVO: Determinar la resistencia a insecticidas en Ae. aegypti y Ae. albopictus de Tapachula, Chiapas, México. MATERIAL Y MÉTODOS: Se utilizaron ovitrampas para obtener huevos de mosquitos Aedes y se realizaron pruebas de susceptibilidad (CDC) y ensayos enzimáticos con la primera generación. RESULTADOS: Aedes aegypti mostró resistencia a deltametrina, permetrina, malatión, clorpirifos, temefos y a bendiocarb (CARB), mientras que Aedes albopictus a malatión y en menor grado a cloripirifos, temefos, permetrina y deltametrina. Ambas especies mostraron altos niveles de enzimas como citocomo P450 y glutatión S-tranferasa, mientras que los niveles de esterasas variaron por especie y sitio muestreado. Se detectó acetilcolinesterasa insensible a insecticidas en ambas especies. CONCLUSIONES: En un hábitat urbano de Tapachula, Chiapas, México donde se aplica control con insecticidas Ae. aegypti y Ae. albopictus sólo son susceptibles al propoxur.

TLR5 participates in the TLR4 receptor complex and promotes MyD88-dependent signaling in environmental lung injury.

Lung disease causes significant morbidity and mortality, and is exacerbated by environmental injury, for example through lipopolysaccharide (LPS) or ozone (O3). Toll-like receptors (TLRs) orchestrate immune responses to injury by recognizing pathogen- or danger-associated molecular patterns. TLR4, the prototypic receptor for LPS, also mediates inflammation after O3, triggered by endogenous hyaluronan. Regulation of TLR4 signaling is incompletely understood. TLR5, the flagellin receptor, is expressed in alveolar macrophages, and regulates immune responses to environmental injury. Using in vivo animal models of TLR4-mediated inflammations (LPS, O3, hyaluronan), we show that TLR5 impacts the in vivo response to LPS, hyaluronan and O3. We demonstrate that immune cells of human carriers of a dominant negative TLR5 allele have decreased inflammatory response to O3 exposure ex vivo and LPS exposure in vitro. Using primary murine macrophages, we find that TLR5 physically associates with TLR4 and biases TLR4 signaling towards the MyD88 pathway. Our results suggest an updated paradigm for TLR4/TLR5 signaling.

Immune cells in the lung help guard against infections. On the surface of these cells are proteins called TLR receptors that recognize dangerous molecules or DNA from disease-causing microbes such as bacteria. When the immune cells detect these invaders, the TLR receptors spring into action and trigger an inflammatory response to destroy the microbes. This inflammation usually helps the lung clear infections. But it can also be harmful and damage the lung, for example when inflammation is caused by non-infectious substances such as pollutants in the atmosphere. There are several TLR receptors that each recognize a specific molecule. In 2010, researchers showed that the receptor TLR4 is responsible for causing inflammation in the lung after exposure to pollution. Another receptor called TLR5 also helps activate the immune response in the lung. But it was unclear whether this receptor also plays a role in pollution-linked lung damage. Now, Hussain, Johnson, Sciurba et al. ­ including one of the researchers involved in the 2010 study ­ have investigated the role of TLR5 in immune cells from the lungs of humans and mice. The experiments showed that TLR5 works together with TLR4 and helps trigger an inflammatory response to both pollutants and bacteria. Hussain et al. found that people lacking a working TLR5 receptor (which make up 3­10% of the population) are less likely to experience lung inflammation when exposed to pollution or bacterial proteins that activate TLR4. These findings suggest that people without TLR5 may be protected from pollution-induced lung injury. Further research into the role of TLR5 could help develop genetic tests for identifying people who are more sensitive to damage from pollution. This information could then be used to determine the likelihood of a patient experiencing certain lung diseases.

Global genetic diversity of Aedes aegypti.

Mosquitoes, especially Aedes aegypti, are becoming important models for studying invasion biology. We characterized genetic variation at 12 microsatellite loci in 79 populations of Ae. aegypti from 30 countries in six continents, and used them to infer historical and modern patterns of invasion. Our results support the two subspecies Ae. aegypti formosus and Ae. aegypti aegypti as genetically distinct units. Ae. aegypti aegypti populations outside Africa are derived from ancestral African populations and are monophyletic. The two subspecies co-occur in both East Africa (Kenya) and West Africa (Senegal). In rural/forest settings (Rabai District of Kenya), the two subspecies remain genetically distinct, whereas in urban settings, they introgress freely. Populations outside Africa are highly genetically structured likely due to a combination of recent founder effects, discrete discontinuous habitats and low migration rates. Ancestral populations in sub-Saharan Africa are less genetically structured, as are the populations in Asia. Introduction of Ae. aegypti to the New World coinciding with trans-Atlantic shipping in the 16th to 18th centuries was followed by its introduction to Asia in the late 19th century from the New World or from now extinct populations in the Mediterranean Basin. Aedes mascarensis is a genetically distinct sister species to Ae. aegypti s.l. This study provides a reference database of genetic diversity that can be used to determine the likely origin of new introductions that occur regularly for this invasive species. The genetic uniqueness of many populations and regions has important implications for attempts to control Ae. aegypti, especially for the methods using genetic modification of populations.