Biology subjects

Bartholomay, L.

Publications and source records attributed to Bartholomay, L..

3 recordsLinked to original sources

bioRxiv2022

Extracellular vesicles secreted by Brugia malayi microfilariae modulate the melanization pathway in the mosquito host

Vector-borne, filarial nematode diseases represent a significant and affecting disease burden in humans, domestic animals, and livestock worldwide. Parasitic filarial nematodes require both an intermediate (vector) host and a definitive (mammalian) host during the course of their life cycle. In either host, the nematode must evade the host elicited immune response in order to develop and establish infection. There is direct evidence of parasite-derived immunomodulation in mammals, however, there is less evidence of parasite immunomodulation of the vector host. We have previously reported that all life stages of Brugia malayi, a causative agent of lymphatic filariasis, secrete extracellular vesicles (EVs). Here we investigate the immunomodulatory effects of microfilariae derived EVs on the vector host Aedes aegypti. RNA-seq analysis of an A. aegypti cell line treated with B. malayi microfilariae EVs showed differential expression of both mRNAs and miRNAs, some with roles in immune regulation. One downregulated gene, AAEL002590, identified as a serine protease, was shown to have direct involvement in the phenoloxidase (PO) cascade through analysis of PO activity. Similarly, injection of adult female mosquitoes with B. malayi microfilariae EVs validated these results in vivo, eliciting a downregulation of the AAEL002590 transcript and a significant reduction in PO activity. Our data indicates that parasite-derived EVs are capable of interfering with critical immune responses in the vector host, particularly immune responses such as melanization that target extracellular parasites. In addition, this data provides novel targets for transmission control strategies for LF and other parasitic diseases. Author SummaryVector-borne, filarial nematode diseases represent a significant and affecting disease burden in humans, domestic animals and livestock worldwide. Parasitic nematodes must evade the elicited immune response of their hosts in order to develop and establish infection. While there is evidence for immunomodulation of the mammalian host, the mechanism of this immunomodulation is not fully clear and there is limited evidence for immunomodulation of the vector host. Here we have shown that parasite-derived extracellular vesicles are effector structures for immunomodulation of the vector host. In particular, we have identified that parasite-derived extracellular vesicles can interfere with critical mosquito immune responses against parasites. This data provides insight into parasite biology and novel targets for transmission control strategies for parasitic diseases.

immunology↗

bioRxiv2021

Leishmania infantum xenodiagnosis from vertically infected dogs reveals significant skin tropism

BackgroundDogs are the primary reservoir for human visceral leishmaniasis due to Leishmania infantum. Phlebotomine sand flies maintain zoonotic transmission of parasites between dogs and humans. A subset of dogs is infected transplacentally during gestation, but at what stage of the clinical spectrum vertically infected dogs contribute to the infected sand fly pool is unknown. Methodology/Principal FindingsWe examined infectiousness of dogs vertically infected with L. infantum from multiple clinical states to the vector Lutzomyia longipalpis using xenodiagnosis and found that vertically infected dogs were infectious to sand flies at differing rates. Dogs with moderate disease showed significantly higher transmission to the vector than dogs with very mild or severe disease. We documented a substantial parasite burden in the skin of vertically infected dogs by RT-qPCR, despite these dogs not having received intradermal parasites via sand flies. There was a highly significant correlation between skin parasite burden at the feeding site and sand fly parasite uptake. This suggests dogs with high skin parasite burden contribute the most to the infected sand fly pool. Although skin parasite load and parasitemia correlated with one another, the average parasite number detected in skin was significantly higher compared to blood in matched subjects. Thus, dermal resident parasites were infectious to sand flies from dogs without detectable parasitemia. Conclusions/SignificanceTogether, our data implicate skin parasite burden and earlier clinical status as stronger indicators of outward transmission potential than blood parasite burden. Our studies of a population of dogs without vector transmission highlights the need to consider canine vertical transmission in surveillance and prevention strategies. AUTHOR SUMMARYSand flies transmit Leishmania parasites between infected dogs and humans leading to the life-threatening tropical disease Visceral Leishmaniasis (VL). Identifying which dogs transmit parasites well to sand flies is important to curb disease spread. The offspring of both dogs and humans can also be infected vertically while in utero. Despite this, the infectiousness of dogs that receive parasites in utero to sand flies has not been thoroughly investigated. Thus, we allowed sand flies to feed on a group of vertically infected dogs at varying stages of VL disease severity and measured sand fly parasite uptake. We found vertically infected dogs were readily able to transmit parasites to the sand flies. Dogs that were most infectious had moderate clinical disease and relatively high levels of parasite infection in their blood and skin. However, the level of skin infection was significantly higher than that observed in the blood, and the skin parasite load had the strongest correlation with sand fly parasite uptake. This implicates the skin may be an underappreciated driver of canine infectiousness to the sand fly vector. In addition, this work highlights that vertically infected dogs are very important parts of the transmission cycle and must be considered in all public health efforts addressing VL.

microbiology↗

bioRxiv2018

Chemosensory structure and function in the filarial nematode, Brugia malayi.

Nematode chemosensory behaviors underlie fundamental processes and activities in development, reproduction, tropisms and taxes. For parasitic species, chemosensation is essential for host seeking and host and tissue invasion behaviors. Such fundamental biology presents an attractive target for developing behavior-blocking anthelminthic drugs, but the anatomy and functional relevance of parasitic nematode chemosensory machinery are poorly understood. The goals of this study were to better understand the chemosensory apparatus and behaviors of infectious stage Brugia malayi (Spirurida: Onchocercidae), a mosquito-borne nematode and etiological agent of Lymphatic Filariasis. Scanning electron microscopy revealed that amphids, the major chemosensory organs, are present on adult B. malayi and arranged in a conserved manner. Internal sensory neuroanatomy display structural differences between life stages, and a simpler chemosensory architecture as compared to free-living nematodes. Positive and negative chemotactic behaviors were identified for a repertoire of chemicals with known chemostimulatory activity for the mosquito host that may facilitate host-selectivity and invasion. This is the first description of chemosensory anatomy and chemotactic behaviors in B. malayi that reveal the involvement of chemosensation in parasite transmission and host invasion.\n\nO_LSTKey findingsC_LST* Amphidial arrangement in B. malayi is less complex than free-living nematodes.\n* Chemosensory neuroanatomy is stage-specific and simpler than free-living nematodes.\n* B. malayi responses to stimuli can be measured using a plate-based assay.\n* Chemostimulants associated with mosquito host-seeking induce negative and positive tropisms for L3 stage B. malayi.

microbiology↗