Biology subjects

Fonseca, D. M.

Publications and source records attributed to Fonseca, D. M..

8 recordsLinked to original sources

bioRxiv2026

Age-dependent disease tolerance to SARS-CoV-2 infection

Disease tolerance limits infectious disease severity through tissue damage control mechanisms that do not target pathogens directly. Here we demonstrate that age-dependent decline in adipose tissue lipolysis compromises disease tolerance to SARS-CoV-2 infection. Young adult mice exhibited robust adipocyte lipolysis and 80% survival, whereas old mice showed impaired adipocyte lipolysis and only 20% survival. Genetic repression of adipocyte lipolysis eliminated this age-dependent survival advantage without affecting viral titers, revealing that adipocyte lipolysis is essential for disease tolerance to SARS-CoV-2 in young adults. Impaired adipocyte lipolysis in aged mice was associated with a plasma lipidomic signature that predicts COVID-19 severity and mortality in three independent human cohorts. Mechanistically, adipocyte lipolysis provides free fatty acids (FFA) to support bone marrow emergency myelopoiesis, through CD36- and CPT1-dependent FFA cellular uptake and mitochondrial import, respectively. Bone marrow derived monocytes migrate to the lung via CCL2/CCR2-dependent mechanism where they enforce an immune-metabolic communication network with parenchymal cells to sustain lung structure and function. This circuit is not required to confer protection against influenza infection, revealing pathogen-specific disease tolerance mechanisms. These findings reveal adipose tissue catabolism as a central age-dependent factor responsible for exacerbated COVID-19 mortality in aged populations. One-Sentence SummarySARS-CoV-2 infection induces adipose tissue lipolysis to release fatty acids that drive myelopoiesis and monocyte production for lung protection and COVID-19 disease tolerance, but this protective circuit declines with age, increasing disease severity in the elderly.

immunology↗

bioRxiv2023

Piroplasm parasites (Apicomplexa: Piroplasmida) in northeastern populations of the invasive Asian longhorned tick, Haemaphysalis longicornis Neumann (Ixodida: Ixodidae), in the United States

Piroplasms, which include the agents of cattle fever and human and dog babesiosis, are a diverse group of blood parasites of significant veterinary and medical importance. The invasive Asian longhorned tick, Haemaphysalis longicornis, is a known vector of piroplasms in its native range in east Asia and invasive range in Australasia. In the US state of Virginia, H. longicornis has been associated with Theileria orientalis Ikeda outbreaks that caused cattle mortality. We examined 667 H. longicornis collected in 2021 from three sites in New Brunswick, New Jersey, the US state where established populations of this species were first detected in 2017. We used primers targeting the 18S small subunit rRNA and the cytochrome b oxidase loci and unveiled the presence of DNA from an unidentified Theileria species (in 1 nymph) and Theileria cervi type F (1 adult, 5 nymphs). In addition, we sequenced a 130 bp fragment of the cytochrome oxidase b locus from Odocoileus virginianus, the white-tailed deer, in a partially engorged questing H. longicornis, supporting the association of this tick species with deer. We also detected DNA from an undescribed Babesia sensu stricto ( true Babesia, 2 adults, 2 nymphs) as well as Babesia sp. Coco (1 adult, 1 nymph). Finally, we detected DNA from Babesia microti S837 (1 adult, 4 nymphs). Babesia microti S837 has been sequenced from striped skunks, Mephitis mephitis, and is closely related to the human pathogen B. microti US-type. The five parasites we are associating with H. longicornis represent a diverse assemblage spanning three clades in the piroplasm phylogeny, two undescribed, raising concerns of transmission amplification of veterinary pathogens as well as spillover of pathogens from wildlife to humans.

ecology↗

bioRxiv2023

Ticks (Acari: Ixodida) on synanthropic small and medium-sized mammals in areas of the northeastern United States infested with the Asian longhorned tick, Haemaphysalis longicornis

The northeastern United States is a hot spot for tick-borne diseases. Adding to an already complex vector landscape, in 2017 large populations of the invasive Haemaphysalis longicornis, the Asian longhorned tick, were detected in New Jersey (NJ) and later found to be widespread from Connecticut to Georgia. In its native range in northeastern Asia, H. longicornis is considered an important vector of deadly pathogens to humans, companion animals, and livestock. To identify the primary hosts of H. longicornis we surveyed synanthropic small and medium-sized mammals in three different sites in suburban New Brunswick, NJ. Specifically, we collected approximately 9,000 tick specimens belonging to nine species from 11 different species of mammals sampled between May and September 2021. We found that H. longicornis feeds more frequently on rodents than previously thought, and that this invasive tick is likely exposed to important enzootic and zoonotic pathogens. Overall, we obtained detailed information about the seasonal dynamics and feeding patterns of six tick species common in the northeastern US, Haemaphysalis longicornis, Amblyomma americanum, Dermacentor variabilis, Ixodes scapularis, I. texanus and I. cookei. We found that unlike I. scapularis that feeds on mammals of all sizes, H. longicornis feeds on hosts following the general pattern of A. americanum, favoring larger species such as skunks, groundhogs, and raccoons. However, our survey revealed that unlike A. americanum, H. longicornis reaches high densities on Virginia opossum. Overall, the newly invasive H. longicornis was the most abundant tick species both on multiple host species and in the environment, raising significant questions regarding its role in the epidemiology of tick-borne pathogens, especially those affecting livestock, companion animals and wildlife. In conclusion, our findings provide valuable insights into the tick species composition on mammal hosts in New Jersey and the ongoing national expansion of H. longicornis.

ecology↗

bioRxiv2022

Transcriptional response of individual Hawaiian Culex quinquefasciatus mosquitoes to the avian malaria parasite Plasmodium relictum

Culex quinquefasciatus, the mosquito vector of avian malaria in Hawai{square}i, became established in the islands in the 1820s and the deadly effects of malaria on endemic bird species have been documented for many decades. To evaluate the gene expression response of the mosquito to the parasite, we let the offspring of wild-collected Hawaiian Cx. quinquefasciatus feed on a domestic canary infected with Plasmodium relictum GRW4 freshly isolated from a wild-caught Hawaiian honeycreeper. Control mosquitoes were fed on an uninfected canary. We sequenced the individual transcriptomes of five infected and three uninfected individual mosquitoes at three different stages of the parasite life cycle: 24 h post feeding (hpf) during ookinete invasion; 5 days post feeding (dpf) when oocysts are developing; 10 dpf when sporozoites are released and invade the salivary glands. Differential gene expression analyses showed that during ookinete invasion (24 hpf), genes related to oxidoreductase activity and galactose catabolism had lower expression levels in infected mosquitoes compared to controls. Oocyst development (5 dpf) was associated with reduced expression of a gene with a predicted innate immune function. At 10 dpf, infected mosquitoes had reduced expression levels of a serine protease inhibitor. Overall, the gene expression response of Hawaiian Culex exposed to a Plasmodium infection intensity that occur naturally in Hawaii was low, but more pronounced during ookinete invasion. The low fitness costs often documented in Culex infected with avian Plasmodium likely reflect the relatively small transcriptional changes observed in mosquito genes related to immune response and nutrient metabolism.

microbiology↗

bioRxiv2021

The Gulf Coast tick, Amblyomma maculatum (Ixodida: Ixodidae) and spotted fever group Rickettsia in the highly urbanized northeastern US

We report the multi-year collection of the Gulf Coast tick, Amblyomma maculatum Koch (Acaridae: Ixodida: Ixodidae) in Staten Island, New York City (NYC) as well as their detection in Brooklyn, NYC, and in Atlantic and Cumberland counties in southern NJ, USA. The first detections on all sites were of adults but in Freshkills Park on Staten Island larvae were collected in a following year. Based on known observations on birds of this tick species, it is likely A. maculatum are expanding north on migratory birds, which are now often seen in Freshkills Park. The presence of larvae indicates that adults are being successful at finding hosts in Staten Island. We describe the landscape features of the area in Staten Island where populations were highest and larvae were detected, which could have facilitated the establishment of A. maculatum. Notably, we also report the presence of human pathogens Rickettsia parkeri in 5/10 (50%) of adults tested and R. felis in 1/24 (4.17%) of larvae tested. In addition to established populations in Staten Island we found evidence of A. maculatum in NJ and other NYC boroughs, suggesting current or future establishment is possible. The failure thus far to detect established populations in these areas may be due to inherent difficulties in detecting low density, spatially heterogeneous incipient populations, which could require targeted surveillance efforts for this species. We discuss the consequences to public health of the establishment of A. maculatum and detection of two additional rickettsial pathogens in the densely populated Northeastern US.

ecology↗

bioRxiv2021

SARS-CoV-2 Infection Impacts Carbon Metabolism and Depends on Glutamine for Replication in Syrian Hamster Astrocytes

Coronaviruses belong to a well-known family of enveloped RNA viruses and are the causative agent of the common cold. Although the seasonal coronaviruses do not pose a threat to human life, three members of this family, i.e., SARS-CoV, MERS-CoV and recently, SARS-CoV2, may cause severe acute respiratory syndrome and lead to death. Unfortunately, COVID-19 has already caused more than 4.4 million deaths worldwide. Although much is better understood about the immunopathogenesis of the lung disease, important information about systemic disease is still missing, mainly concerning neurological parameters. In this context, we sought to evaluate immunometabolic changes using in vitro and in vivo models of hamsters infected with SARS-CoV-2. Here we show that, besides infecting hamsters astrocytes, SARS-CoV-2 induces changes in protein expression and metabolic pathways involved in carbon metabolism, glycolysis, mitochondrial respiration, and synaptic transmission. Interestingly, many of the differentially expressed proteins are concurrent with proteins that correlate with neurological diseases, such as Parkinsonss disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntingtons disease. Metabolic analysis by high resolution real-time respirometry evidenced hyperactivation of glycolysis and mitochondrial respiration. Further metabolomics analysis confirmed the consumption of many metabolites, including glucose, pyruvate, glutamine, and alpha ketoglutarate. Interestingly, we observed that glutamine was significantly reduced in infected cultures, and the blockade of mitochondrial glutaminolysis significantly reduced viral replication and pro-inflammatory response. SARS-CoV-2 was confirmed in vivo as hippocampus, cortex, and olfactory bulb of intranasally infected hamsters were positive for viral genome several days post-infection. Altogether, our data reveals important changes in overall protein expression, mostly of those related to carbon metabolism and energy generation, causing an imbalance in important metabolic molecules and neurotransmitters. This may suggest that some of the neurological features observed during COVID-19, as memory and cognitive impairment, may rely on altered energetic profile of brain cells, as well as an unbalanced glutamine/glutamate levels, whose importance for adequate brain function is unquestionable.

immunology↗

bioRxiv2021

A gene-based capture assay for surveying patterns of genetic diversity and insecticide resistance in a worldwide group of invasive mosquitoes

Understanding patterns of diversification, genetic exchange, and pesticide resistance in insect species of human health concern is necessary for effective population reduction and management. With the broad availability of next-generation sequencing technologies, one of the best approaches for surveying such patterns involves the simultaneous genotyping of many samples for large numbers of genetic markers from across the known genome. To this end, the targeting of gene sequences of known function or inheritance can be a cost-effective strategy. One insect group of substantial health concern are the mosquito taxa that make up the Culex pipiens complex. Members of this complex transmit damaging arboviruses and filariae worms to humans, as well as other pathogens that are detrimental to endangered vertebrate species such as bird malaria. Here we describe our development of a targeted gene-based assay for surveying genetic diversity and population structure in this mosquito complex. To test the utility of this assay, we examined taxonomic divergence among samples from several members of the complex, as well as distinct populations of the relatively under-studied Culex quinquefasciatus, an urban pantropical species. We also examined the presence of known insecticide-resistance conferring alleles. Broadly, our developed gene-based assay proved effective for examining patterns of taxonomic and geographic clustering within the species complex, as well as for surveying genetic variants that have been associated with insecticide resistance. This assay will be useful for future studies that aim to understand the genetic mechanisms underlying the evolution of ubiquitous and increasingly damaging disease vectors.

genomics↗

bioRxiv2019

Coordination among neighbors improves the efficacy of Zika control despite economic costs

BackgroundEmerging mosquito-borne viruses like Zika, dengue, and chikungunya pose a major threat to public health, especially in low-income regions of Central and South America, southeast Asia, and the Caribbean. Outbreaks of these diseases are likely to have long-term social and economic consequences due to Zika-induced congenital microcephaly and other complications. Larval control of the container-inhabiting mosquitoes that transmit these infections is an important tool for mitigating outbreaks. However, metapopulation theory suggests that spatiotemporally uneven larvicide treatment can impede control effectiveness, as recolonization compensates for mortality within patches. Coordinating the timing of treatment among patches could therefore substantially improve epidemic control, but we must also consider economic constraints, since coordination may have costs that divert resources from treatment.\n\nMethodology/Principle FindingsTo inform practical disease management strategies, we ask how coordination among neighbors in the timing of mosquito control efforts influences the size of a mosquito-borne infectious disease outbreak under the realistic assumption that coordination has costs. Using an SIR/metapopulation model of mosquito and disease dynamics, we examine whether larvicide treatment triggered by surveillance information from neighboring patches reduces human infections when incorporating coordination costs. We examine how different types of coordination costs and different surveillance methods jointly influence the effectiveness of larval control. We find that the effect of coordination depends on both costs and the type of surveillance used to inform treatment. With epidemiological surveillance, coordination improves disease outcomes, even when costly. With demographic surveillance, coordination either improves or hampers disease control, depending on the type of costs and surveillance sensitivity.\n\nConclusions/SignificanceOur results suggest coordination among neighbors can improve management of mosquito-borne epidemics under many, but not all, assumptions about costs. Therefore, estimating coordination costs is an important step for most effectively applying metapopulation theory to strategies for managing outbreaks of mosquito-borne viral infections.\n\nAuthor SummaryMosquito-borne viruses, such as Zika, are an urgent public health threat, particularly in tropical, low-income regions. Vector control, the main strategy for combatting outbreaks, can be challenging because the urban-adapted, container-breeding mosquitoes that transmit these viruses often exhibit metapopulation dynamics, where mortality in one population is compensated by migration from neighboring populations. The timing and spatial distribution of vector control efforts can therefore have a large impact on their efficacy. Using a model of virus transmission and vector population dynamics, we demonstrate that local mosquito control initiatives aimed at reducing the burden of Zika and other mosquito-borne infections are most effective when there is communication of surveillance findings among neighboring control agencies and coordination over the timing of mosquito reduction treatments. We find that local communication improves epidemic outcomes even when it imposes costs to resource-limited control agencies due to gains in the efficiency of mosquito control from spatial coordination.

ecology↗