Matthew Rogers

Matthew Rogers
London School of Hygiene and Tropical Medicine | LSHTM · Department of Immunology and Infection

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64
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Publications

Publications (64)
Article
Full-text available
Direct glycan–glycan interactions are increasingly implicated in survival and pathogenicity of bacteria. Here, we show that they can be exploited by protozoan parasites in their insect hosts. Force spectroscopy revealed that Leishmania promastigotes display a high-affinity biomolecular interaction between their lipophosphoglycan glycocalyx and mimi...
Article
Full-text available
Leishmania parasites are transmitted to vertebrate hosts by female phlebotomine sand flies as they bloodfeed by lacerating the upper capillaries of the dermis with their barbed mouthparts. In the sand fly midgut secreted proteophosphoglycans from Leishmania form a biological plug known as the promastigote secretory gel (PSG), which blocks the gut a...
Data
PSG does not influence scratch wound healing to cultured keratinocytes. Monolayers of Kera308 keratinocytes were scratched in the presence of culture media supplemented with or without 0.5 μg/ml L. mexicana PSG. Positive controls were treated with 10 μg/ml TGFβ2 and 10 μg/ml EGF. A) At 0, 12 and 24 hours post-wound, photomicrographs were taken and...
Data
PSG promotes JAK-STAT signalling. STAT3-Luciferase reporter HeLa cells were exposed to 1 μg PSG ± 1:100 anti-IGF1R Ab for 24 hours. Positive controls were treated with 1 ng/ml and 10 ng/ml Oncostatin M for 8 hours. Luciferase expression was recorded with a luminomter. Results are from a representative experiment. Relative light intensity is present...
Data
Gene Ontology enrichment analysis of genes influenced by PSG in skin. (DOCX)
Data
PSG augments the wound response during L. mexicana infection. Ears of BALB/c mice were intra-dermally inoculated with 1 x 103 L. mexicana metacyclic promastigotes ±0.5 μg L. mexicana PSG or PBS. A-C) Six hours post-infection ears were measured for transcripts involved in the inflammation and cell proliferation phases of wound healing by real-time q...
Data
PSG augments the production of chemokines and cytokines involved in the early wound response during L. mexicana infection. Ears of BALB/c mice were intra-dermally inoculated with 1 x 103 L. mexicana metacyclic promastigotes ±0.5 μg L. mexicana PSG or PBS. A and B) Twenty four hours post-infection ears were measured for proteins involved in the infl...
Data
Top 168 canonical pathways influenced by PSG in skin. Results of IPA of 5,312 genes of known function modulated by PSG (cut off ≥ FC5 at 5% FDR). (DOCX)
Data
RTqPCR primer sequences and melting temperatures used in this study. The genes used to validate gene expression in the microarray study (Fig 1E) are denoted with an asterisk. (DOCX)
Data
PSG promotes IL-17a production in skin at the bite site 6 hours post-infection. Ears of BALB/c mice were intra-dermally inoculated with 1 x 103 L. mexicana metacyclic promastigotes ±0.5 μg/ml L. mexicana PSG. IL-17a production was determined from whole cell lysates using Luminex. Data is representative duplicate experiments (*: p<0.05 by Mann Whitn...
Article
Full-text available
Visceral Leishmaniasis (VL) is a neglected vector-borne disease. In India, it is transmitted to humans by Leishmania donovani-infected Phlebotomus argentipes sand flies. In 2005, VL was targeted for elimination by the governments of India, Nepal and Bangladesh by 2015. The elimination strategy consists of rapid case detection, treatment of VL cases...
Article
Parasitic infections such as Leishmania induce a cascade of host physiological responses, including metabolic and immunological changes. Infection with Leishmania major protozoa causes cutaneous leishmaniasis in humans, a neglected tropical disease with suboptimal disease management. To understand the determinants of pathology, we studied L. major...
Chapter
Full-text available
Leishmaniasis is a ‘ neglected tropical disease neglected tropical disease’, and there have been some significant recent advances in research on how Leishmania Leishmania species, the causative agents of the disease, affect the behaviour of phlebotomine sandfly sandflies, their insect vectors. This chapter briefly describes the eco-epidemiology of...
Article
Full-text available
Leishmania are transmitted by the bite of their sand fly vector and this has a significant influence on the virulence of the resulting infection. From our studies into the interaction between parasite, vector, and host we have uncovered an important missing ingredient during Leishmania transmission. Leishmania actively adapt their sand fly hosts in...
Article
Cutaneous leishmaniasis (CL) is a neglected tropical disease that causes prominent skin scaring. No water soluble, non-toxic, short course and low cost treatment exists. We developed a new water soluble amphotericin B-polymethacrylic acid (AmB-PMA) using established and scalable chemistries. AmB-PMA was stable for 9 months during storage. In vitro,...
Article
Full-text available
Background: Visceral leishmaniasis is the world' second largest vector-borne parasitic killer and a neglected tropical disease, prevalent in poor communities. Long-lasting insecticidal nets (LNs) are a low cost proven vector intervention method for malaria control; however, their effectiveness against visceral leishmaniasis (VL) is unknown. This st...
Article
Full-text available
Visceral leishmaniasis is the world' second largest vector-borne parasitic killer and a neglected tropical disease, prevalent in poor communities. Long-lasting insecticidal nets (LNs) are a low cost proven vector intervention method for malaria control; however, their effectiveness against visceral leishmaniasis (VL) is unknown. This study quantifi...
Chapter
This chapter briefly discusses the leishmaniasis model. The leishmaniases are a group of vector-borne parasitic diseases that represent a major international public health problem; they belong to the most neglected tropical diseases, are major causes of morbidity and mortality and impede economic development especially in the developing world. The...
Article
There is an urgent need for a non-toxic and low-cost treatment for cutaneous leishmaniasis. We synthesised and tested in vivo an amphotericin B-poly(methacrylic acid) drug (AmB-PMA) that had previously shown in-vitro activity against Leishmania major and L. donovani parasites. Efficacy was determined using L. major footpad infection in 30 non-heali...
Article
We demonstrate that a proteophosphoglycan-rich gel secreted by Leishmania infantum inside the midgut of Lutzomyia longipalpis sand flies (promastigote secretory gel) is regurgitated along with an average dose of 500 L. infantum metacyclic promastigotes per infected bite. Using both low (10³) and high (10⁵) doses of parasites in the ears of BALB/c m...
Article
Full-text available
Anthroponotic visceral leishmaniasis, transmitted by Phlebotomus argentipes Annandale & Brunetti (Diptera: Psychodidae) sand flies, is regarded as a major problem of public health importance in the Indian subcontinent. Understanding the feeding behavior of the vector can be used to investigate changes in human-vector contact during intervention pro...
Data
Supplementary Table 1: Comparison of Indian and Nepalese household sand fly densities and anti-saliva antibody levels. During the KALANET study sand flies were sampled monthly by CDC light trap for 15 months in households from control clusters (i.e. no bed nets and no insecticide house spraying) from VL endemic areas. Peak season sand fly densities...
Article
Full-text available
Antibody (IgG) responses to the saliva of Phlebotomus argentipes were investigated using serum samples from regions of India endemic and non-endemic for visceral leishmaniasis (VL). By pre-adsorbing the sera against the saliva of the competing human-biting but non-VL vector P. papatasi, we significantly improved the specificity of a P. argentipes s...
Article
Full-text available
All natural Leishmania infections start in the skin; however, little is known of the contribution made by the sand fly vector to the earliest events in mammalian infection, especially in inflamed skin that can rapidly kill invading parasites. During transmission sand flies regurgitate a proteophosphoglycan gel synthesized by the parasites inside th...
Data
Co-incubation with PSG enhances the proportion of L. mexicana-hosting macrophages in vitro, under a range of activation states. (A–D) Kinetic of infected BALB/c bone marrow-derived macrophages in the presence or absence of classical activators and vector-derived products. (A) Control L. mexicana infections of PBS (unstimulated, open circles), IFNγ...
Data
PSG does not influence the phagocytosis of L. mexicana in vitro. (A&B) Unstimulated, alternatively activated (AA) and classically activated (CA) BALB/c BMMΦ were infected with L. mexicana metacyclic promastigotes at MOI 5∶1 in the presence or absence of 1 µg/ml L. mexicana PSG, 1 µg/ml Lu. longipalpis saliva, 1 µg/ml PSG and saliva or PBS control f...
Data
The arginase inhibitor nor-NOHA does not affect L. mexicana amastigote and promastigote growth and development in vitro. Lesion amastigotes were seeded into culture at 1×106/ml and 5×105/ml for axenic amastigote and promastigote cultures, respectively. (A and B) Growth kinetics of amastigotes (A) or promastigotes (B) grown in culture media with (cl...
Data
PSG enhances the viability of L. mexicana inside air pouch macrophages and neutrophils in vivo. Cells recruited to BALB/c air pouches inoculated with 1×106 L. mexicana metacyclic promastigotes with (closed symbols) or without (open symbols) 1 µg L. mexicana PSG for 48 hours were recovered, washed and plated on plastic to harvest adherent macrophage...
Data
Co-incubation with PSG enhances the viability of L. mexicana inside macrophages in vitro. The viability of parasites obtained from 5×104 unstimulated, AA and CA macrophages, in the presence or absence of 0.25 µg L. mexicana PSG was assessed 48 hour after infection by labeling with fluorescence. Amastigotes released from macrophages were transformed...
Data
Key features of L. mexicana amastigote and promastigote growth and development in vitro are unaffected by the presence of the arginase inhibitor nor-NOHA. Promastigote and amastigote growth was observed for 8 days and the mean population doubling time (PDT) (fast parasite growth is reflected by a low PDT) was determined from 4 cultures per conditio...
Data
PSG does not influence macrophage phagosome-lysosome fusion during L. mexicana infection in vitro. (A–L) Confocal microscopy of phagosome-lysosome fusion after 4 hours infection with red fluorescent L. mexicana parasites (L. mexicana dsRed, MOI 5∶1) in unstimulated BMMΦ (A–D), CAMΦ (E–H) and AAMΦ (I–L). Late endosomes are labelled blue and lysosome...
Data
PSG increases the alternative activation of macrophages. 5×105 unstimulated, alternatively activated BALB/c macrophages were incubated in the presence or absence of 0.25 µg L. mexicana PSG for 48 hours. Surface expression of murine mannose receptor, CD206 was determined by flow cytometry using a FACSCalibur (Becton Dickinson). Representative data i...
Article
Full-text available
The amino acid L-arginine plays a crucial role in the regulation of immune responses. We have recently shown that uncontrolled replication of Leishmania parasites at the site of pathology correlates with high levels of arginase activity in nonhealing leishmaniasis and that this elevated arginase activity causes local depletion of L-arginine. To fur...
Article
Full-text available
The balance between T helper (Th) 1 and Th2 cell responses is a major determinant of the outcome of experimental leishmaniasis, but polarized Th1 or Th2 responses are not sufficient to account for healing or nonhealing. Here we show that high arginase activity, a hallmark of nonhealing disease, is primarily expressed locally at the site of patholog...
Data
Sensitivity of (A) Leishmania kDNA and (B) DNA polymerase α gene primers. Ethidium-bromide-stained PCR products separated on 1.75% (w/v) wide range agarose gels in Tris-acetate buffer for serial 10-fold dilutions of Le. infantum DNA (lanes 2–10) using (A) kDNA or (B) DNA polymerase primers. Lane 1: 50 bp DNA ladder (MBI Fermentas); lane 2: 100 ng;...
Data
Specificity of (A) Leishmania DNA polymerase α and (B) Lutzomyia longipalpis periodicity gene primers. Ethidium-bromide-stained PCR products separated on 1.75% (w/v) wide range agarose gels in Tris-acetate buffer alongside a 50 bp DNA ladder (Fermentas); lane 1 in both panels. (A) PCR with Leishmania DNA polymerase primers. Lanes 2–11: serial 10-fo...
Article
Chitinases of trypanosomatid parasites have been proposed to fulfil various roles in their blood-feeding arthropod vectors but so far none have been directly tested using a molecular approach. We characterized the ability of Leishmania mexicana episomally transfected with LmexCht1 (the L. mexicana chitinase gene) to survive and grow within the perm...
Article
Leishmania chagasi, transmitted mainly by Lutzomyia longipalpis sand flies, causes visceral leishmaniasis and atypical cutaneous leishmaniasis in Latin America. Successful vector control depends upon determining vectorial capacity and understanding Leishmania transmission by sand flies. As microscopic detection of Leishmania in dissected sand fly g...
Data
Blood Meal Volume Obtained by Uninfected Sand Flies Five-day-old flies were exposed individually to a single anaesthetized mouse and the relative size of their blood meal obtained (none, partial, or full) after one feeding attempt was recorded upon dissection. (37 KB DOC)
Data
Effect of L. mexicana Infection on Blood Meal Volume Obtained by Sand Flies All flies were infected with 2 × 106 lesion amastigotes per ml rabbit blood by membrane feeding. Flies with 4- to 10-d-old infections were exposed individually to a single anaesthetized mouse and the relative size of their blood meal obtained (none, partial, or full) after...
Data
Effect of L. infantum Infection on Blood Meal Volume Obtained by Sand Flies All flies were infected with 2 × 106 splenic amastigotes per ml rabbit blood by membrane feeding. Flies with 4- to 10-d-old infections were exposed individually to a single anaesthetized mouse and the relative size of their blood meal obtained (none, partial, or full) after...
Data
Effect of Leishmania Infection and Environmental Stress Conditions on Sand Fly Fecundity A total of 50 female flies per group were dissected to determine the number of eggs they produced 4 d following infection or blood feeding. A further total of 50 female flies per group were allowed to lay eggs in oviposition pots for 7 d at which time the numbe...
Article
Full-text available
In nature the prevalence of Leishmania infection in whole sand fly populations can be very low (<0.1%), even in areas of endemicity and high transmission. It has long since been assumed that the protozoan parasite Leishmania can manipulate the feeding behavior of its sand fly vector, thus enhancing transmission efficiency, but neither the way in wh...
Data
BLASTN against Bacteria _DB database
Data
Results of BLASTN against CDS of L. major with E < 10−25
Data
Matches with UniProt database and Drosophila and Anopheles proteins
Article
Full-text available
An expressed sequence tag library has been generated from a sand fly vector of visceral leishmaniasis, Lutzomyia longipalpis. A normalized cDNA library was constructed from whole adults and 16,608 clones were sequenced from both ends and assembled into 10,203 contigs and singlets. Of these 58% showed significant similarity to known genes from other...
Article
Full-text available
Leishmaniasis is a vectorborne disease transmitted to human and other mammalian hosts by sand fly bite. In the present study, we show that immunization with Leishmania mexicana promastigote secretory gel (PSG) or with a chemically defined synthetic glycovaccine containing the glycans found in L. mexicana PSG can provide significant protection again...
Article
In this study, disease progression after intravenous or subdermal infection of dogs with Leishmania infantum JPC strain was monitored. A challenge performed on 14 dogs via the intravenous route with 5 x 10(7) stationary phase promastigotes of the L. infantum JPC strain was 100% successful. During a follow up period of 1.5 years, several parameters...
Article
Full-text available
Chitinases have been implicated to be of importance in the life cycle development and transmission of a variety of parasitic organisms. Using a molecular approach, we identified and characterized the structure of a single copy LmexCht1-chitinase gene from the primitive trypanosomatid pathogen of humans, Leishmania mexicana. The LmexCht1 encodes an...
Article
Leishmania alternates between two main morphological forms in its life cycle: intracellular amastigotes in the mammalian host and motile promastigotes in the sandfly vector. Several different forms of promastigote can be recognised in sandfly infections. The first promastigote forms, which are found in the sandfly in the bloodmeal phase, are multip...
Article
Full-text available
Sand flies are the exclusive vectors of the protozoan parasite Leishmania, but the mechanism of transmission by fly bite has not been determined nor incorporated into experimental models of infection. In sand flies with mature Leishmania infections the anterior midgut is blocked by a gel of parasite origin, the promastigote secretory gel. Here we a...
Article
The life cycle of Leishmania alternates between two main morphological forms: intracellular amastigotes in the mammalian host and motile promastigotes in the sand fly vector. Several different forms of promastigote have been described in sandfly infections, the best known of these being metacyclic promastigotes, the mammal-infective stages. Here we...
Article
Full-text available
Transmission of leishmaniasis is effected by a specific developmental stage, the metacyclic promastigote. The precursors of metacyclic promastigotes were a distinct subpopulation of parasites, identified for the first time as a new stage in the life-cycle and named leptomonad promastigotes. Microdissection of infected sandflies into 4 midgut region...
Article
The effects of root herbivory on a tephritid seed predator (Terellia ruficauda) and its parasitoids were investigated. Soil fauna were manipulated by insecticide treatment; host plant (Cirsium palustre) phenology and the oviposition behaviour of both tephritid and parasitoids (Pteromalus elevatus and Torymus chloromerus) recorded. Although insectic...
Article
Development of Leishmania parasites in the digestive tract of their sandfly vectors involves several morphological transformations from the intracellular mammalian amastigote via a succession of free and gut wall-attached promastigote stages to the infective metacyclic promastigotes. At the foregut midgut transition of Leishmania-infected sandflies...