Biology subjects

Serafim, T. D.

Publications and source records attributed to Serafim, T. D..

4 recordsLinked to original sources

bioRxiv2025

Discovery of an Adaptive Neuroimmune Response Driving Itch and Fast Tick Removal with Implications for Preventing Pathogen Transmission

Acquired tick resistance (ATR) is well characterized in tick-exposed animals, compromising tick fitness through antibody-mediated activation of basophils. Yet, anti-tick vaccines inducing ATR have had limited success. Here, we describe a neuroimmune event preceding ATR that leads to rapid host-mediated tick removal. Tick-sensitized guinea pigs mechanically remove ticks within 3-6 hours via an acquired neuroimmune-induced itch response that correlates with increased dermal expression of itch-associated genes like OSM and skin infiltration by T cells and macrophages, independently of IgG and IgE antibodies. When we expose humans to ticks, a similar immune response is observed. Blocking T cells before tick sensitization prevents immune cell infiltration to bite sites and abrogates scratching and tick removal. This neuroimmune response is independent of Trpv1 as tick-sensitized guinea pigs treated with resiniferatoxin remove ticks effectively. Itch-induced tick removal or IITR offers a novel approach to tick-borne disease prevention through early tick detection and removal.

neuroscience↗

bioRxiv2022

Genetic exchange in Leishmania is facilitated by IgM natural antibodies

Host factors mediating Leishmania genetic exchange are not well defined. Here, we demonstrate that IgM antibodies, but not IgG or IgA, facilitate parasite genetic hybridization in vitro and in vivo. IgM induces the gradual and transient formation of a structured parasite clump in a process essential for L. major and L. tropica hybridization in vitro. Parasite hybrids and 3-nucleated parasites were observed inside this structure, named the Leishmania mating clump. IgM was also required for or significantly increased Leishmania hybrid formation in vivo. At minimum, we observed a 12-fold increase in the proportion of hybrids recovered from sand flies provided a second blood meal containing IgM compared to controls. Notably, genetic backcross events in sand flies were only observed in the presence of IgM, and were reproducibly recovered, reinforcing the relevance of IgM for Leishmania genetic exchange in vivo. The in vitro and in vivo Leishmania crosses from these studies resulted in full genome hybrids. Leishmania co-option of a host antibody to facilitate mating in the insect vector establishes a new paradigm of parasite-host-vector coevolution that promotes parasite diversity and fitness through genetic exchange.

microbiology↗

bioRxiv2019

Leishmania infection induces a limited differential gene expression in the sand fly midgut

BackgroundPhlebotomine sand flies are the vectors of Leishmania worldwide. To develop in the sand fly midgut, Leishmania multiplies and undergoes multiple stage differentiations leading to the infective form, the metacyclic promastigotes. To gain a better understanding of the influence of Leishmania infection in midgut gene expression, we performed RNA-Seq comparing uninfected Lutzomyia longipalpis midguts and Leishmania infantum-infected Lutzomyia longipalpis midguts at seven time points which cover the various developmental Leishmania stages including early time points when blood digestion is taking place and late time points when the parasites are undergoing metacyclogenesis. ResultsOut of over 13,841 transcripts assembled de novo, only 113 sand fly transcripts, about 1%, were differentially expressed. Further, we observed a low overlap of differentially expressed sand fly transcripts across different time points suggesting a specific influence of each Leishmania stage on midgut gene expression. Two main patterns of sand fly gene expression modulation were noticed. At early time points (days 1-4), more transcripts were down-regulated by Leishmania infection at large fold changes (> -32 fold). Among the down-regulated genes, the transcription factor Forkhead/HNF-3 and hormone degradation enzymes were differentially regulated on day 4 and appear to be the upstream regulators of nutrient transport, digestive enzymes, and peritrophic matrix proteins. Conversely, at later time points (days 6 onwards), most of the differentially expressed transcripts were up-regulated by small fold changes (< 32 fold), and the molecular function of such genes are associated with the metabolism of lipids and detoxification of xenobiotics (P450). ConclusionOverall, it appears that Leishmania modulates sand fly gene expression early on in order to overcome the barriers imposed by the midgut, yet it behaves like a commensal at later time points, when modest midgut gene expression changes correlate with a massive amount of parasites in the anterior midgut.

microbiology↗

bioRxiv2019

Distinct gene expression patterns in vector-residing Leishmania infantum identify parasite stage-enriched markers

Promastigotes of Leishmania infantum undergo a series of extracellular developmental stages inside the natural sand fly vector Lutzomyia longipalpis to reach the infectious stage, the metacyclic promastigote. There is limited information regarding the expression profile of L. infantum developmental stages inside the sand fly vector, and molecular markers that can distinguish the different parasite stages are lacking. We performed RNAseq on unaltered midguts of the sand fly Lutzomyia longipalpis after infection with L. infantum parasites. RNAseq was carried out at various time points throughout parasite development. Principal component analysis mapped the sequences corresponding to the procyclic, nectomonad, leptomonad or metacyclic promastigote stage into distinct positions, with the procyclic stage being the most divergent population. Transcriptional levels across genes varied on average between 10- to 100-fold. Comparison between procyclic and nectomonad promastigotes resulted in 836 differentially expressed (DE) genes; between nectomonad and leptomonad promastigotes in 113 DE genes; and between leptomonad and metacyclic promastigotes in 302 DE genes. Most of the DE genes do not overlap across stages, highlighting the uniqueness of each stage. Furthermore, the different stages of Leishmania parasites exhibited specific transcriptional enrichment across chromosomes. Using the transcriptional signatures exhibited by distinct Leishmania stages during their development in the sand fly midgut, we determined the genes predominantly enriched in each stage, identifying multiple stage-specific markers for L. Infantum. Leading stage-specific marker candidates include genes encoding a zinc transporter in procyclics, a beta-fructofuranidase in nectomonads, a surface antigen-like protein in leptomonads, and an amastin-like surface protein in metacyclics. Overall, these findings demonstrate the transcriptional plasticity of the Leishmania parasite inside the sand fly vector and provide a repertoire of stage-specific markers for further development as molecular tools for epidemiological studies.

microbiology↗