Impaired LAIR-1-mediated immune control due to collagen degradation in fibrosis.

Tissue repair is disturbed in fibrotic diseases like systemic sclerosis (SSc), where the deposition of large amounts of extracellular matrix components such as collagen interferes with organ function. LAIR-1 is an inhibitory collagen receptor highly expressed on tissue immune cells. We questioned whether in SSc, impaired LAIR-1-collagen interaction is contributing to the ongoing inflammation and fibrosis. We found that SSc patients do not have an intrinsic defect in LAIR-1 expression or function. Instead, fibroblasts from healthy controls and SSc patients stimulated by soluble factors that drive inflammation and fibrosis in SSc deposit disorganized collagen products in vitro, which are dysfunctional LAIR-1 ligands. This is dependent of matrix metalloproteinases and platelet-derived growth factor receptor signaling. In support of a non-redundant role of LAIR-1 in the control of fibrosis, we found that LAIR-1-deficient mice have increased skin fibrosis in response to repeated injury and in the bleomycin mouse model for SSc. Thus, LAIR-1 represents an essential control mechanism for tissue repair. In fibrotic disease, excessive collagen degradation may lead to a disturbed feedback loop. The presence of functional LAIR-1 in patients provides a therapeutic opportunity to reactivate this intrinsic negative feedback mechanism in fibrotic diseases.

First national record of Aedes melanimon (Diptera: Culicidae) in Mexico.

Aedes (Ochlerotatus) melanimon Dyar 1924 has been considered an important pest in agricultural and rural communities. Aedes melanimon is a vector of WEEV and CEV and is a competent laboratory vector of WNV. The known range of Ae. melanimon extends throughout Southwest Canada, part of Central and most of Western USA. Here we report the first record of Ae. melanimon in Mexico, at Ciudad Juárez, Chihuahua. The collect represents the southernmost distributional record for this species. Its indigenous presence in a highly urbanized and dry area was not expected. A permanent surveillance program to detect and determine the species in border-crossing cities is encouraged.

New records of Triatoma huehuetenanguensis in an urban area of Southwest Mexico.

The recently described Triatoma huehuetenanguensis, has been reported in Mexico, Guatemala, Belize and Honduras. In Mexico, the species has been collected primarily in rural areas; it has the potential to colonize human dwellings, however, its contribution to Chagas outbreaks remains unclear. In 2021, T. huehuetenanguensis was first observed at Tuxtla Gutierrez city, Chiapas; then a collection for the species was performed. A total of 308 houses were inspected in the intra and peridomestic structures. Only 3 houses (0.97%) were infested. Triatoma huehuetenangensis was the only triatomine specie recorded and four males were collected. None of the bugs tested positive for Trypanosoma infection. We do not have evidence to suggest that urban human-vector contact still limited, and a possible domestication process is possible. The presence of reservoirs, the vector species and the parasite demonstrate that Tuxtla Gutierrez could be at risk of a Chagas disease outbreak.

COVID-19 and its impact on the control of Aedes (Stegomyia) aegypti mosquito and epidemiological surveillance of arbovirus infections.

In American countries, simultaneously with the coronavirus disease 2019 (COVID-19) pandemic, epidemics caused by different arboviruses (dengue, chikungunya and Zika viruses) are occurring. In Mexico, several of the strategies to control the Aedes aegypti mosquito, which transmits arboviruses, involve the interaction of health personnel with the community. Due to the COVID-19 pandemic, social distancing and home confinement measures have been implemented. To obey these measures and avoid the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, the National Center for Preventive Programs and Disease Control (CENAPRECE) has presented the vector control strategy in the scenario of simultaneous dengue and COVID-19 transmission in Mexico. In this work, we mention the routine comprehensive mosquito control measures and describe the adaptations that have been made. Furthermore, we discuss the relevance of medical personnel training and supervision, especially focusing on the similarity of symptoms between both pathologies.

En países americanos, simultáneas a la pandemia de enfermedad por coronavirus 2019 (COVID-19) se están dando epidemias ocasionadas por diferentes arbovirus (del dengue, chikunguña y virus del Zika). En México, varias de las estrategias para control del mosquito Aedes aegypti, transmisor de arbovirus, involucran la interacción del personal salubrista y los moradores. Debido a la pandemia de COVID-19 se han implementado medidas de distanciamiento social y resguardo domiciliario. Para respetar estas medidas y evitar riesgo de contagio por coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2), el Centro Nacional de Programas Preventivos y Control de Enfermedades (CENAPRECE) ha presentado la estrategia de control de vectores en el escenario de transmisión simultánea por dengue y COVID-19 en México. En este trabajo mencionamos las medidas habituales de manejo integral de mosquito y mencionamos las adaptaciones realizadas. De igual forma, discutimos la relevancia de la capacitación y la supervisión al personal médico, esto debido a la similitud entre la sintomatología entre ambas patologías.

Experimental infection and vector competence of Zika virus in Aedes aegypti mosquitoes from Acapulco, Guerrero, Mexico.

OBJECTIVE: To gain a better understanding of the Zika virus (ZIKV) vector transmission in Mexico, we determined the vector competence of a local population of Ae. aegypti (Acapulco, Guerrero) for a strain of ZIKV isolated from a Mexican febrile patient. MATERIALS AND METHODS: Eggs were hatched and larvae were reared under controlled conditions. After five days post-emergence, female mosquitoes were fed an infectious blood-meal containing ZIKV. Mosquitoes were analyzed at 4, 7 and 14-day post-infection (dpi). Infection (gut), dissemination (wings, legs and heads) and potential transmission (salivary glands) were assessed by RT-qPCR. The Rockefeller Ae. aegypti strain was used as ZIKV infection control. RESULTS: ZIKV infection, dissemination, and potential transmission rates were 96.2, 96.1 and 93.2%, respectively. CONCLUSIONS: Ae. aegypti (F1) from Acapulco were very susceptible to ZIKV infection, and showed similar vector competence to that of the susceptible Rockefeller strain. To our knowledge, this is the first report of vector competence for ZIKV performed in a Mexican laboratory.

OBJETIVO: Determinar la competencia vectorial de una población local de Ae. aegypti para transmitir el virus Zika (ZIKV) aislado de un paciente febril mexicano. MATERIAL Y MÉTODOS: Se desarrolló la primera generación (F1) de mosquitos Ae. aegypti en el insectario a partir de huevos colectados mediante ovitrampas en la Colonia Renacimiento, Acapulco, Guerrero. Después de cinco días de la emergencia, los mosquitos hembras fueron alimentados con sangre infecciosa con ZIKV. La infección (intestino), la diseminación (alas, piernas y cabezas) y la transmisión potencial (glándulas salivales) se evaluaron mediante RT-qPCR, a los 4, 7 y 14 días después de la alimentación. RESULTADOS: La infección por ZIKV, la diseminación y las tasas potenciales de transmisión fueron de 96.2, 96.1 y 93.2%, respectivamente. CONCLUSIONES: Los mosquitos Ae. aegypti (F1) de Acapulco presentan una alta competencia vectorial (93.2%). Según los autores de este estudio, este es el primer informe de competencia vectorial para ZIKV realizado en un laboratorio mexicano.

Aedes aegypti, the dengue fever mosquito in Mexico City. Early invasion and its potential risks.

INTRODUCTION: Mexico City has no endemic presence of Aedes aegypti, and it is therefore free of vector-borne diseases, such as dengue fever, Zika and chikungunya. However, evidence has shown the presence of Aedes aegypti eggs in the city since 2015. OBJECTIVE: To report the constant and increasing presence of Aedes aegypti eggs in Mexico City from 2015 to 2018. METHODS: Surveillance was carried out using ovitraps. Eggs were counted and hatched in order to determine the species. RESULTS: From 2015 to 2018, 378 organisms were identified as Ae. aegypti. In total, 76 Aedes aegypti-positive ovitraps were collected at 50 different places in 11 boroughs of the city. Northeastern Mexico City was the area with the highest number of positive traps. CONCLUSIONS: The results may be indicating a period of early colonization and the probable existence of cryptic colonies of the mosquito; Mexico City could be at risk of experiencing vector-borne epidemics.

INTRODUCCIÓN: La Ciudad de México no tiene presencia endémica de Aedes aegypti, por lo que está libre de enfermedades transmitidas por vector como dengue, Zika y chikunguña. Sin embargo, existe evidencia de la presencia de huevecillos en la urbe desde 2015. OBJETIVO: Reportar la presencia constante y en aumento de huevecillos de Aedes aegypti en la Ciudad de México de 2015 a 2018. MÉTODO: Se realizó vigilancia a través de ovitrampas; se contabilizaron y eclosionaron huevecillos para determinar la especie. RESULTADOS: De 2015 a 2018 fueron identificados 378 organismos como Aedes aegypti. En total fueron colectadas 76 ovitrampas positivas a Aedes aegypti en 50 sitios distintos de 11 alcaldías. El noreste de la Ciudad de México fue el área con mayor positividad. CONCLUSIONES: Los resultados pueden estar indicando un periodo de colonización incipiente y la probable la existencia de colonias crípticas del mosquito, por lo que la Ciudad de México podría estar en riesgo de presentar epidemias de enfermedades transmitidas por vector.

Molecular Basis for Arbovirus Transmission by Aedes aegypti Mosquitoes.

Mosquitoes are considered the most important vectors for the transmission of pathogens to humans. Aedes aegypti is a unique species, not only by its highly anthropophilic and peridomestic habits but also because it can transmit an important variety of pathogenic viruses. Examples are dengue, yellow fever, chikungunya, Zika, and Mayaro viruses. After ingesting viremic blood, a wide range of mechanisms are activated in the mosquito to counteract viral infection. Nevertheless, these arboviruses possess strategies to overcome barriers in the mosquito and eventually reach the salivary glands to continue the transmission cycle. However, the infection and eventual transmission of arbovirus depends on multiple factors. The current review focuses in detail on the anatomic, physiological, and molecular characteristics of the mosquito A. aegypti that participate in response to a viral infection. In the past decades, the awareness of the importance of this mosquito as a disease vector and its impact on human health was largely recognized. We need to improve our comprehension of molecular mechanisms that determine the outcome of successful virus replication or control of infection for each arbovirus in the vector; this could lead to the design of effective control strategies in the future.

The CARMA1 signalosome links the signalling machinery of adaptive and innate immunity in lymphocytes.

The recognition of antigen by B- or T-cell receptors initiates an intracellular signalling cascade that results in the nuclear translocation and activation of the transcription factor nuclear factor-kappaB (NF-kappaB). NF-kappaB is an important regulator of lymphocyte development and function, and its dysregulation is associated with many immune disorders. Defining the mechanisms that transmit signals from the antigen receptor to NF-kappaB is therefore an important goal for immunologists. In this Review, we merge information gleaned from research of the innate immune system with what we know about antigen-receptor signals in the adaptive immune system, to propose a cohesive model of how antigen receptors activate NF-kappaB.

West Nile virus in Mexico: Why vectors matter for explaining the current absence of epidemics.

Since 2002, West Nile Virus (WNV) has been reported in 18 states in Mexico, either by PCR or serological testing. However, it is believed that the virus is present in more states. Only four states (out of 32) have reported confirmed human cases, and one state has serological evidence. In the country, WNV is present in mainly horses and birds, but its presence extends to crocodiles, felines, canines, swines, donkeys, caprines, antilopes, cattle, bats, and camelids. Positive mosquito species include Aedes and Culex spp. Different hypotheses have been proposed to explain the absence of WNV epidemics in Latin America. Since some regions of Mexico and the United States share ecological and climatic conditions, these hypotheses may not be sufficient to account for the absence of WNV outbreaks or epidemics. This paper discusses the proposed ideas and attempts to contextualize them for Mexico, particularly for the U.S.-Mexico border, where WNV infections have been reported in humans, horses, and mosquitoes. We propose that integration of urban ecology and entomology knowledge is needed to better understand the absence of WN cases in Mexico.

Programmed Cell Death-1 (PD-1) anchoring to the GPI-linked co-receptor CD48 reveals a novel mechanism to modulate PD-1-dependent inhibition of human T cells.

Activation of PD-1 by anchoring it to Antigen Receptor (AR) components or associated co-receptors represents an attractive approach to treat autoimmune conditions. In this study, we provide evidence that CD48, a common lipid raft and Src kinase-associated coreceptor, induces significant Src kinase-dependent activation of PD-1 upon crosslinking, while CD71, a receptor excluded from these compartments, does not. Functionally, using bead-conjugated antibodies we demonstrate that CD48-dependent activation of PD-1 inhibits proliferation of AR-induced primary human T cells, and similarly, PD-1 activation using PD-1/CD48 bispecific antibodies inhibits IL-2, enhances IL-10 secretion, and reduces NFAT activation in primary human and Jurkat T cells, respectively. As a whole, CD48-dependent activation of PD-1 represents a novel mechanism to fine tune T cell activation, and by functionally anchoring PD-1 with receptors other than AR, this study provides a conceptual framework for rational development of novel therapies that activate inhibitory checkpoint receptors for treatment of immune-mediated diseases.

Serine 649 phosphorylation within the protein kinase C-regulated domain down-regulates CARMA1 activity in lymphocytes.

Phosphorylation of CARMA1 is a crucial event initiating the assembly of IkappaB kinase and JNK signaling complexes downstream of activated Ag receptors. We previously mapped three protein kinase C (PKC) target sites in murine CARMA1 in vitro, and demonstrated that mutation of two of these serines (S564 and S657) resulted in reduced NF-kappaB activation, whereas mutation of the third serine (S649) had no clear effect. In this study, we report that when low concentrations of Ag receptor activators are used, loss of S649 (by mutation to alanine) promotes enhanced IkappaB kinase and JNK activation in both B and T cell lines. Reconstitution of CARMA1(-/-) DT40 B cells with CARMA1 S649A leads to increased cell death and reduced cell growth in comparison to wild-type CARMA1, likely a result of enhanced JNK activation. To directly determine whether S649 is modified in vivo, we generated phospho-specific Abs recognizing phospho-S649, and phospho-S657 as a positive control. Although phospho-S657 peaked and declined rapidly after Ag receptor stimulation, phospho-S649 occurred later and was maintained for a significantly longer period poststimulation in both B and T cells. Interestingly, phospho-S657 was completely abolished in PKCbeta-deficient B cells, whereas delayed phosphorylation at S649 was partially intact and depended, in part, upon novel PKC activity. Thus, distinct PKC-mediated CARMA1 phosphorylation events exert opposing effects on the activation status of CARMA1. We propose that early phosphorylation events at S657 and S564 promote the initial assembly of the CARMA1 signalosome, whereas later phosphorylation at S649 triggers CARMA1 down-regulation.

Genetic variance and genotype-by-environment interaction of immune response in Aedes aegypti (Diptera: Culicidae).

Immune response can be negatively affected by resource limitation, so it is expected that organisms evolve strategies to minimize the impact of this environmental outcome. Phenotypic plasticity in immune response could represent a genetic response to face such situations. We investigated the effects of high and low quality and quantity of food at the larval stage on two important immune components, phenoloxidase activity (PO) and nitric oxide production (NO) measured in adults of the Dengue vector, Aedes aegypti. We reared families to determine the magnitude and pattern of expression of genetic variance, environmental variance and genotype-by-environment interaction (GEI). In addition, we quantified whether there were differences in plastic immune responses in both sexes. Our results indicated additive variance for PO and NO, but rearing environment did not produce differences among individuals. For NO and PO in males, there were large differences among families in plasticity, as indicated by the different slopes produced by each reaction norm. Therefore, there is additive genetic variation in plasticity for NO production and PO activity. One possible interpretation of these results is that different genotypes may be favored to fight pathogens under the different food quality situations. Males and females showed similar overall GEI strategies but there were differences in PO and NO. Males showed a phenotypic correlation between PO and NO, but we did not find genetic correlations between immune parameters in both sexes.

First Record of Aedes gabriel in Hidalgo State, Mexico.

Aedesgabriel is one of the rare species endemic in Mexico. This species was originally described from specimens collected in the state of Morelos in 1970; however, very few occurrence records have been published since. During an ovitrap survey of mosquitoes in 2018, eggs of Ae. gabriel were collected for the 1st time in the state of Hidalgo, Mexico. Aedes gabriel appears to have become common and the species is frequently found in ovitraps, and often confused with other common species of Aedes, such as Ae. epactius, Ae. podographicus, Ae. aegypti, and Ae. albopictus. Females of Ae. gabriel are highly anthropophagous and persistent biters in wild habits during the rainy season. Although the medical importance of Ae. gabriel is unknown, its biting habitats and increasing abundance indicate that the potential importance of this species should not be neglected by the public health officials of Mexico.

First Report of Aedes albopictus in Guerrero State, Mexico.

In 1988, Aedes albopictus was first described in Mexico. Since then, it has been recorded in most of the coastal states that have a shoreline on the Gulf of Mexico, 3 states in Central Mexico and 2 states on the coast of the Pacific Ocean. This is the first report documenting the presence of this invasive species in Guerrero, a state with coastlines on the Pacific Ocean. This evidence suggests that the distribution of Ae. albopictus is expanding throughout Mexico. It remains unknown the extent to which Ae. albopictus contributes to vector-borne disease transmission in this country; however, the risk should not be neglected.

Surveillance for Zika in Mexico: naturally infected mosquitoes in urban and semi-urban areas.

Zika cases have been reported in 29 out of the 32 states of Mexico. Information regarding which mosquito species might be driving Zika virus transmission/maintenance in nature must be regularly updated. From January 2017 to November 2018, mosquitoes were collected indoors and outdoors using the CDC backpack aspirator in urban and semi-urban areas with evidence of mosquito-borne disease transmission. 3873 mosquito pools were tested for Zika infection using the CDC Trioplex real-time RT-PCR. For each collected specie, maximum likelihood estimator of infection rate (MLE) was estimated. Results showed 492 mosquito pools positive for Zika virus RNA. The majority of the positive pools were Aedes (Stegomyia) aegypti (Linnaeus) (54.6%, MLE = 19) (males and females) and Culex (Culex) quinquefasciatus (Say) (19.5%, MLE = 16.8). For the first time, ZIKV infection was detected in Ae. (Georgecraigius) epactius (Dyar and Knab) (MLE = 17.1), Cx. (Melanoconion) erraticus (Dyar and Knab) (MLE = non-estimable), Culiseta (Culiseta) inornata (Williston) (MLE = non estimable), and Cs (Cs.) particeps (Adams) (MLE = 369.5). Other detected species were: Ae. (Stg.) albopictus (Skuse) (MLE = 90.5), Cx. (Cx.) coronator s.l. (Dyar and Knab) (MLE = 102.8) and Cx. (Cx.) tarsalis (Coquillett) (MLE = 117.2). However, our results do not allow for the incrimination of these species as vectors of ZIKV. Routine surveillance should start to consider other mosquito species across the taxonomic spectrum of the Culicidae.

Urban and semi-urban mosquitoes of Mexico City: A risk for endemic mosquito-borne disease transmission.

Since past century, vector-borne diseases have been a major public health concern in several states of Mexico. However, Mexico City continues to be free of endemic mosquito-borne viral diseases. The city is the most important politic and economic state of Mexico and one of the most important city of Latin America. Its subtropical highland climate and high elevation (2240 masl) had historically made the occurrence of Aedes species unlikely. However, the presence of other potential disease vectors (Culex spp, Culiseta spp), and the current intermittent introductions of Aedes aegypti, have revealed that control programs must adopt routine vector surveillance in the city. In this study, we provide an updated species list from a five-years of vector surveillance performed in Mexico City. A total of 18,553 mosquito larvae were collected. Twenty-two species from genus Culex, Aedes, Culiseta, Anopheles, Lutzia and Uranotaenia were observed. Nine new mosquito records for the city were found. Ae. albopictus was recorded for the first time in Mexico City. Interestingly, a new record, Ae. epactius was the most frequent species reported. Cx. pipiens quinquefasciatus exhibited the highest number of individuals collected. We detected six areas which harbor the highest mosquito species records in the city. Cemeteries included 68.9% of our collection sites. Temporarily ponds showed the highest species diversity. We detected an increasing presence of Ae. aegypti, which was detected for three consecutive years (2015-2017), predominantly in the warmer microclimates of the city. We found a possible correlation between increasing temperature and Ae. aegypti and Ae. albopictus expanding range. This study provides a starting point for developing strategies related to environmental management for mosquito control. The promotion of mosquito control practices through community participation, mass media and education programmes in schools should be introduced in the city.

Efficacy of 13 Commercial Household Aerosol Insecticides Against Aedes aegypti (Diptera: Culicidae) From Morelos, Mexico.

In Mexico, Aedes aegypti (L.) (Diptera: Culicidae) is the primary vector of Dengue, Zika, and Chikungunya viruses. Control programs include community participation using personal protection such as household aerosol insecticides. In both, urban or rural areas, the use of aerosol insecticides is a common practice to avoiding mosquito biting. Thus, information on the efficacy of commercial products must be available. This study reports the efficacy of 13 household aerosol insecticides against Ae. aegypti from an endemic dengue area in Mexico. To test each insecticide, six netting cages, containing 10 non-blood fed female mosquitoes each one, were placed in different locations inside a bedroom. Readings at 30 min and 24 h after exposure were recorded. No products showed 100% mortality after 30 min of exposure. Only three products killed the 100% of the individuals 24 h after exposure. Results showed a high mortality variance among insecticides. Location in the room also impacts the insecticide efficacy. Mosquitoes located inside cabinets or with behind an obstacle (preventing an accurate insecticide exposure) showed lower mortalities. Products and spraying methods could and should be improved.

Are body size and volatile blends honest signals in orchid bees?

Secondary sexual traits may convey reliable information about males' ability to resist pathogens and that females may prefer those traits because their genes for resistance would be passed on to their offspring. In many insect species, large males have high mating success and can canalize more resources to the immune function than smaller males. In other species, males use pheromones to identify and attract conspecific mates, and thus, they might function as an honest indicator of a male's condition. The males of orchid bees do not produce pheromones. They collect and store flower volatiles, which are mixed with the volatile blends from other sources, like fungi, sap and resins. These blends are displayed as perfumes during the courtship. In this study, we explored the relationship between inter-individual variation in body size and blend composition with the males' phenoloxidase (PO) content in Euglossa imperialis. PO content is a common measure of insect immune response because melanine, its derived molecule, encapsulates parasites and pathogens. Body size and blend composition were related to bees' phenolic PO content. The inter-individual variation in body size and tibial contents could indicate differences among males in their skills to gain access to some compounds. The females may evaluate their potential mates through these compounds because some of them are reliable indicators of the males' capacity to resist infections and parasites.

Repellency of 29 Synthetic and Natural Commercial Topical Insect Repellents Against Aedes aegypti (Diptera: Culicidae) in Central Mexico.

In Mexico, the use of repellents to prevent insects from landing and biting is a common practice. However, variation in the efficiency of natural and synthetic repellents has been observed. In this study, we evaluated the repellency and protection time of 16 synthetic and 13 natural-based commercial products against Aedes aegypti (L.) from an endemic dengue area (Jojutla, Morelos) in Central Mexico. The "arm exposure" cage test was used to assess the efficacy of the repellents. Tests were conducted by three adult volunteers. Results showed that DEET (N, N-Diethyl-3-methylbenzamide) repellents provided the highest protection and duration times against Ae. aegypti. However, low repellency and short-time protection was observed (when compared with the manufacturers' protection times). Natural-based products did not repel (either landing or biting) mosquitoes for >30 min. These results show that most of the repellent products did not provide satisfactory levels of personal protection against mosquito bites. Frequent reapplication of repellents (synthetic and natural-based) may compensate for their short duration of action. Repellent efficacy data must be integrated into the decision-making process for an optimal response to the local (or specific region) situation.