Biology subjects

Flores, F.

Publications and source records attributed to Flores, F..

4 recordsLinked to original sources

bioRxiv2024

Long-term efficacy of adoptive cell therapy is determined by host CD8+ T cells and undermined by lymphodepleting preconditioning

Adoptive T cell therapy (ACT) has demonstrated remarkable efficacy in treating hematological cancers. However, its efficacy against solid tumors remains limited and the emergence of cancer cells that lose expression of targeted antigens often promotes resistance to ACT. Importantly, the mechanisms underlying effective and durable ACT-mediated tumor control are incompletely understood. Here, we show that adoptive transfer of TCR-transgenic CD8+ T cells eliminates established murine melanoma tumors, with concomitant accumulation of tumor-infiltrating CD8+ T cells exhibiting both progenitor-exhausted and terminally-differentiated phenotypes. Interestingly, host CD8+ T cells contributed to ACT-mediated elimination of primary tumors and rejected ACT-resistant melanoma cells lacking the targeted antigen. Mechanistically, ACT induced TNF-- and cross-presenting dendritic cell-dependent tumor accumulation of endogenous CD8+ T cells and effective tumor elimination. Importantly, although lymphodepleting preconditioning enhanced ACT-mediated tumor elimination, it abrogated host antitumor immunity and protection against ACT-resistant melanoma cells. Enrichment of transcriptional signatures associated with TNF- signaling, cross-presenting dendritic cells and tumor-specific CD8+ T cells in human melanoma tumors correlated with favorable responses to ACT and increased survival. Our findings reveal that long-term efficacy of ACT is determined by the interplay between transferred and endogenous CD8+ T cells and is undermined by lymphodepleting preconditioning, which ultimately favors ACT resistance.

immunology↗

bioRxiv2019

Culex saltanensis and Culex interfor (Diptera: Culicidae) are susceptible and competent to transmit St. Louis encephalitis virus (Flavivirus: Flaviviridae) in central Argentina.

AO_SCPLOWBSTRACTC_SCPLOWInfectious diseases caused by mosquito-borne viruses constitute health and economic problems worldwide. St. Louis encephalitis virus (SLEV) is endemic and autochthonous in the American continent. Culex pipiens quinquefasciatus is the primary urban vector of SLEV; however, Culex interfor and Culex saltanensis have also been found naturally infected with the virus, suggesting their potential role as vectors. OBJECTIVEThe aim of this study was to determine the vector competence of Cx. interfor and Cx. saltanensis for SLEV from central Argentina in comparison to Cx. p. quinquefasciatus. METHODSAdult female mosquitoes of the three Culex species were orally infected by feeding on viremic chicks that had been inoculated with SLEV. Then, abdomens, legs and saliva blood-fed mosquitoes were analyzed by viral plaque assay and the presence of cytopathic effect on the cell culture monolayer. RESULTSMosquitoes were permissive to orally acquired infections, to virus dissemination, and transmission of SLEV in the saliva. Cx. saltanensis and Cx. interfor are potential vectors of SLEV. CONCLUSIONSOur results demonstrate that in Argentina both Cx. saltanensis and Cx. interfor are susceptible to SLEV and competent for its transmission. Moreover they are abundant during SLEV epidemic period in urban area, positive for this virus in nature, and found to feed on natural hosts. This article has been peer-reviewed and recommended by Peer Community in Entomology

microbiology↗

bioRxiv2019

Characterization of a new cytorhabdovirus discovered in papaya (Carica papaya) plantings of Ecuador and its relationship with a bean-infecting strain from Brazil

The complete genome of a new rhabdovirus infecting papaya (Carica papaya L.) was sequenced and characterized. The genome consists of 13,469 nucleotides with six canonical open reading frames (ORFs) predicted from the antigenomic strand. In addition, two overlapping short ORFs were predicted between ORFs 3 and 4. Phylogenetic analyses using amino acid sequences from the nucleocapsid, glycoprotein and polymerase, grouped the virus with members of the genus Cytorhabdovirus, with rice stripe mosaic virus, yerba mate chlorosis-associated virus and Colocasia bobone disease-associated virus as closest relatives. The 3 leader and 5 trailer sequences were 144 and 167 nt long, respectively. Each end contains complementary sequences prone to form panhandle structures. The motif 3-AUUCUUUUUG-5, conserved across rhabdoviruses, was identified in all but one intergenic regions; whereas the motif 3-ACAAAAACACA-5 was found in three intergenic junctions. This is the first complete genome of a cytorhabdovirus infecting papaya. The virus was prevalent in commercial plantings of Los Rios, the most important papaya producing province of Ecuador. During the final stage of this manuscript preparation, the genome of a bean-associated cytorhabdovirus became available. Nucleotide identity (97%) between both genomes indicated that the two viruses are strains of the same species, for which we propose the name papaya cytorhabdovirus E.

microbiology↗

bioRxiv2018

Seasonal changes in diet and toxicity in the Climbing Mantella frog (Mantella laevigata)

Poison frogs acquire chemical defenses from the environment for protection against potential predators. These defensive chemicals are lipophilic alkaloid toxins that are sequestered by poison frogs from dietary arthropods and stored in skin glands. Despite decades of research focusing on identifying poison frog toxins, we know relatively little about how environmental variation and subsequent arthropod availability impacts toxicity in poison frogs. We investigated how seasonal environmental variation influences poison frog toxin profiles through changes in the diet of the Climbing Mantella (Mantella laevigata). We collected M. laevigata females on the Nosy Mangabe island reserve in Madagascar during the wet and dry seasons and tested the hypothesis that seasonal differences in rainfall is associated with changes in the diet and skin toxin profiles of M. laevigata. The arthropod diet of each frog was characterized into five groups (i.e. ants, termites, mites, insect larvae, or other) using visual identification and cytochrome oxidase 1 DNA barcoding. We found that frog diet differed between the wet and dry seasons, where frogs had a more diverse diet in the wet season and consumed a higher percentage of ants in the dry season. To determine if seasonality was associated with variation in frog defensive chemical composition, we used gas chromatography / mass spectrometry to quantify toxins from individual skin samples. Although the assortment of identified toxins was similar across seasons, we detected significant differences in the abundance of certain alkaloids, which we hypothesize reflects seasonal variation in the diet of M. laevigata. We suggest that these variations could originate from seasonal changes in either arthropod leaf litter composition or changes in frog behavioral patterns. Although additional studies are needed to understand the consequences of long-term environmental shifts, this work suggests that toxin profiles are relatively robust against short-term environmental perturbations.

ecology↗