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

2019 ◽  
Author(s):  
Iliano V. Coutinho-Abreu ◽  
Tiago D. Serafim ◽  
Claudio Meneses ◽  
Shaden Kamhawi ◽  
Fabiano Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Early Time ◽  
Differentially Expressed ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Lutzomyia Longipalpis ◽  
Late Time ◽  
Blood Digestion ◽  
Time Points

Abstract Background: Phlebotomine 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. Results: Out 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). Conclusion: Overall, 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.

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

2019 ◽  
Author(s):  
Iliano V. Coutinho-Abreu ◽  
Tiago D. Serafim ◽  
Claudio Meneses ◽  
Shaden Kamhawi ◽  
Fabiano Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Early Time ◽  
Differentially Expressed ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Lutzomyia Longipalpis ◽  
Late Time ◽  
Blood Digestion ◽  
Time Points

AbstractBackgroundPhlebotomine 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.

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

2020 ◽  
Author(s):  
Iliano V. Coutinho-Abreu ◽  
Tiago D. Serafim ◽  
Claudio Meneses ◽  
Shaden Kamhawi ◽  
Fabiano Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Developmental Stages ◽  
De Novo ◽  
Early Time ◽  
Differentially Expressed ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Lutzomyia Longipalpis ◽  
Late Time ◽  
Time Points

Abstract Background: Phlebotomine 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 on midgut gene expression, we performed RNA-Seq comparing uninfected and Leishmania infantum -infected Lutzomyia longipalpis midguts at seven time points which cover the various Leishmania developmental stages including early time points when blood digestion is taking place, and late time points when the parasites are undergoing metacyclogenesis. Results: Out 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 that each Leishmania stage influences midgut gene expression in a specific manner. Two main patterns of sand fly gene expression modulation were noted. 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). The molecular function of these genes has been associated with the metabolism of lipids and detoxification of xenobiotics. Conclusion: Overall, 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, where a massive number of parasites in the anterior midgut results only in modest changes in midgut gene expression.

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

2020 ◽  
Author(s):  
Iliano V. Coutinho-Abreu ◽  
Tiago D. Serafim ◽  
Claudio Meneses ◽  
Shaden Kamhawi ◽  
Fabiano Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Early Time ◽  
Differentially Expressed ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Developmental Cycle ◽  
Lutzomyia Longipalpis ◽  
Sand Flies ◽  
Time Points

Abstract Background: Sand flies are the vectors of Leishmania parasites. To develop in the sand fly midgut, Leishmania multiplies and undergoes various stage differentiations giving rise to the infective form, the metacyclic promastigotes. To determine the changes in sand fly midgut gene expression caused by the presence of Leishmania, we performed RNA-Seq of uninfected and Leishmania infantum-infected Lutzomyia longipalpis midguts from seven different libraries corresponding to time points which cover the various Leishmania developmental stages. Results: The combined transcriptomes resulted in the de novo assembly of 13,841 sand fly midgut transcripts. Importantly, only 113 sand fly transcripts, about 1%, were differentially expressed in the presence of Leishmania parasites. Further, we observed distinct differentially expressed sand fly midgut transcripts corresponding to the presence of each of the various Leishmania stages suggesting that each parasite stage influences midgut gene expression in a specific manner. Two main patterns of sand fly gene expression modulation were noted. 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 2 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 Leishmania infection with small fold changes (< 32 fold). The molecular functions of these genes have been associated with the metabolism of lipids and detoxification of xenobiotics. Conclusion: Overall, our data suggest that the presence of Leishmania produces a limited change in the midgut transcript expression profile in sand flies. Further, Leishmania modulates sand fly gene expression early on in the developmental cycle in order to overcome the barriers imposed by the midgut, yet it behaves like a commensal at later time points where a massive number of parasites in the anterior midgut results only in modest changes in midgut gene expression.

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

2020 ◽  
Author(s):  
Iliano V. Coutinho-Abreu ◽  
Tiago D. Serafim ◽  
Claudio Meneses ◽  
Shaden Kamhawi ◽  
Fabiano Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Early Time ◽  
Differentially Expressed ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Developmental Cycle ◽  
Lutzomyia Longipalpis ◽  
Sand Flies ◽  
Time Points

Abstract Background: Sand flies are the vectors of Leishmania parasites. To develop in the sand fly midgut, Leishmania multiplies and undergoes various stage differentiations giving rise to the infective form, the metacyclic promastigotes. To determine the changes in sand fly midgut gene expression caused by the presence of Leishmania, we performed RNA-Seq of uninfected and Leishmania infantum-infected Lutzomyia longipalpis midguts from seven different libraries corresponding to time points which cover the various Leishmania developmental stages. Results: The combined transcriptomes resulted in the de novo assembly of 13,841 sand fly midgut transcripts. Importantly, only 113 sand fly transcripts, about 1%, were differentially expressed in the presence of Leishmania parasites. Further, we observed distinct differentially expressed sand fly midgut transcripts corresponding to the presence of each of the various Leishmania stages suggesting that each parasite stage influences midgut gene expression in a specific manner. Two main patterns of sand fly gene expression modulation were noted. 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 2 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 Leishmania infection with small fold changes (< 32 fold). The molecular functions of these genes have been associated with the metabolism of lipids and detoxification of xenobiotics. Conclusion: Overall, our data suggest that the presence of Leishmania produces a limited change in the midgut transcript expression profile in sand flies. Further, Leishmania modulates sand fly gene expression early on in the developmental cycle in order to overcome the barriers imposed by the midgut, yet it behaves like a commensal at later time points where a massive number of parasites in the anterior midgut results only in modest changes in midgut gene expression.

scholarly journals DISTINCT CELLULAR MIGRATION INDUCED BY Leishmania infantum chagasi AND SALIVA FROM Lutzomyia longipalpis IN A HEMORRHAGIC POOL MODEL

2014 ◽  
Vol 56 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Camila Oliveira Vasconcelos ◽  
Zirlane C. Branco Coelho ◽  
Cristina de Souza Chaves ◽  
Clarissa Romero Teixeira ◽  
Margarida M. Lima Pompeu ◽  
...  
Keyword(s):  
Cell Population ◽  
Cellular Migration ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Lutzomyia Longipalpis ◽  
Specific Cell ◽  
Air Pouch ◽  
Leukocyte Accumulation ◽  
Pool Model ◽  
Sand Fly Vectors

Recruitment of a specific cell population after Leishmania infection can influence the outcome of the disease. Cellular migration in response to Leishmania or vector saliva has been reported in air pouch model, however, cellular migration induced by Leishmania associated with host's blood and vector saliva in this model has not been described. Herein we investigated cellular migration into air pouch of hamster after stimulation with combination of L. chagasi and host's blood and Lutzomyia longipalpis saliva. Migration induced by saliva was 3-fold more than those induced by L. chagasi alone. Additionally, L. chagasi associated with blood and saliva induced significantly even more leukocytes into air pouch than Leishmania alone. L. chagasi recruited a diverse cell population; however, most of these cells seem to have not migrated to the inflammatory exudate, remaining in the pouch lining tissue. These results indicate that L. chagasi can reduce leukocyte accumulation to the initial site of infection, and when associated with vector saliva in the presence of blood components, increase the influx of more neutrophils than macrophages, suggesting that the parasite has developed a strategy to minimize the initial inflammatory response, allowing an unlimited progression within the host. This work reinforces the importance of studies on the salivary components of sand fly vectors of leishmaniasis in the transmission process and the establishment of the infection.

scholarly journals Differential Histopathology and Chemokine Gene Expression in Lung Tissues following Respiratory Syncytial Virus (RSV) Challenge of Formalin-Inactivated RSV- or BBG2Na-Immunized Mice

2001 ◽  
Vol 75 (24) ◽  
pp. 12421-12430 ◽  
Author(s):  
Ultan F. Power ◽  
Thierry Huss ◽  
Vincent Michaud ◽  
Hélène Plotnicky-Gilquin ◽  
Jean-Yves Bonnefoy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Respiratory Syncytial Virus ◽  
Mouse Model ◽  
Subunit Vaccine ◽  
Late Time ◽  
Chemokine Gene ◽  
Time Points ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Chemokine Gene Expression

ABSTRACT A BALB/c mouse model of enhanced pulmonary pathology following vaccination with formalin-inactivated alum-adsorbed respiratory syncytial virus (FI-RSV) and live RSV challenge was used to determine the type and kinetics of histopathologic lesions induced and chemokine gene expression profiles in lung tissues. These data were compared and contrasted with data generated following primary and/or secondary RSV infection or RSV challenge following vaccination with a promising subunit vaccine, BBG2Na. Severe peribronchiolitis and perivascularitis coupled with alveolitis and interstitial inflammation were the hallmarks of lesions in the lungs of FI-RSV-primed mice, with peak histopathology evident on days 5 and 9. In contrast, primary RSV infection resulted in no discernible lesions, while challenge of RSV-primed mice resulted in rare but mild peribronchiolitis and perivascularitis, with no evidence of alveolitis or interstitial inflammation. Importantly, mice vaccinated with a broad dose range (20 to 0.02 μg) of a clinical formulation of BBG2Na in aluminium phosphate demonstrated histopathology similar to that observed in secondary RSV infection. At the molecular level, FI-RSV priming was characterized by a rapid and strong up-regulation of eotaxin and monocyte chemotactic protein 3 (MCP-3) relative gene expression (potent lymphocyte and eosinophil chemoattractants) that was sustained through late time points, early but intermittent up-regulation of GRO/melanoma growth stimulatory activity gene and inducible protein 10 gene expression, while macrophage inflammatory protein 2 (MIP-2) and especially MCP-1 were up-regulated only at late time points. By comparison, primary RSV infection or BBG2Na priming resulted in considerably lower eotaxin and MCP-3 gene expression increases postchallenge, while expression of lymphocyte or monocyte chemoattractant chemokine genes (MIP-1β, MCP-1, and MIP-2) were of higher magnitude and kinetics at early, but not late, time points. Our combined histopathologic and chemokine gene expression data provide a basis for differentiating between aberrant FI-RSV-induced immune responses and normal responses associated with RSV infection in the mouse model. Consequently, our data suggest that BBG2Na may constitute a safe RSV subunit vaccine for use in seronegative infants.

Entomological Studies in Itaúna, Brazil, an Area With Visceral Leishmaniasis Transmission: Fauna Survey, Natural Leishmania Infection, and Molecular Characterization of the Species Circulating in Phlebotomine Sand Flies (Diptera: Psychodidae)

2019 ◽  
Vol 56 (5) ◽  
pp. 1368-1376 ◽  
Author(s):  
Josiane V Lopes ◽  
Erika M Michalsky ◽  
Nathalia C L Pereira ◽  
Adão J V de Paula ◽  
Fabiana O Lara-Silva ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Natural Infection ◽  
Local Population ◽  
Influential Factor ◽  
Sand Fly ◽  
Health Concern ◽  
Leishmania Infection ◽  
Lutzomyia Longipalpis ◽  
Sand Flies ◽  
Phlebotomine Sand Flies

Abstract Among neglected tropical diseases, visceral leishmaniasis (VL) shows great relevance in global terms and is a serious public health concern due to the possibility of severe and lethal forms in humans. In this study, we evaluate entomological factors such as diversity and abundance of phlebotomine sand flies (Diptera:Psychodidae) and the Leishmania species circulating in these species in possible association with VL transmission in the Brazilian town Itaúna. The entomological collections were performed during three consecutive nights, always in the third week of each month, within a period of 12 mo. A total of 1,786 sand fly specimens were collected, from which 20% were collected inside houses. The influence of three local climatic variables (temperature, rainfall, relative humidity) on the population sizes of these insects was evaluated. Temperature was the most influential factor, with a significant positive correlation with the local population size of phlebotomine sand flies collected per month. Lutzomyia longipalpis (Lutz & Neiva, 1912) was the predominant species in the study area. Leishmania DNA was detected in nine out of 133 pools of sand fly females, using nested/PCR, which resulted in a minimal natural infection rate of 2.91%. DNA from Leishmania infantum Nicolle, 1908 (Kinetoplastida: Trypanosomatida), was detected in Evandromyia cortelezzii (Bréthes, 1923), Ev. evandroi (Costa, Lima & Antunes, 1936), Ev. lenti (Mangabeira, 1938), and Ev. termitophila (Martins, Falcão & Silva, 1964), besides Lu. longipalpis. Our study indicates favorable conditions for VL spreading in Itaúna due to the presence of Lu. longipalpis and Le. infantum-infected phlebotomine sand flies.

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

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Iliano V. Coutinho-Abreu ◽  
Tiago Donatelli Serafim ◽  
Claudio Meneses ◽  
Shaden Kamhawi ◽  
Fabiano Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Differential Gene

scholarly journals Kaposi's Sarcoma-Associated Herpesvirus Induces Sustained NF-κB Activation during De Novo Infection of Primary Human Dermal Microvascular Endothelial Cells That Is Essential for Viral Gene Expression

2007 ◽  
Vol 81 (8) ◽  
pp. 3949-3968 ◽  
Author(s):  
Sathish Sadagopan ◽  
Neelam Sharma-Walia ◽  
Mohanan Valiya Veettil ◽  
Hari Raghu ◽  
Ramu Sivakumar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
De Novo ◽  
Viral Gene Expression ◽  
Angiogenic Factors ◽  
Viral Gene ◽  
Kshv Infection ◽  
Time Points ◽  
Lytic Genes

ABSTRACT In vitro Kaposi's sarcoma-associated herpesvirus (KSHV) infection of primary human dermal microvascular endothelial (HMVEC-d) cells and human foreskin fibroblast (HFF) cells is characterized by the induction of preexisting host signal cascades, sustained expression of latency-associated genes, transient expression of a limited number of lytic genes, and induction of several cytokines, growth factors, and angiogenic factors. Since NF-κB is a key molecule involved in the regulation of several of these factors, here, we examined NF-κB induction during de novo infection of HMVEC-d and HFF cells. Activation of NF-κB was observed as early as 5 to 15 min postinfection by KSHV, and translocation of p65-NF-κB into nuclei was detected by immunofluorescence assay, electrophoretic mobility shift assay, and p65 enzyme-linked immunosorbent assay. IκB phosphorylation inhibitor (Bay11-7082) reduced this activation significantly. A sustained moderate level of NF-κB induction was seen during the observed 72 h of in vitro KSHV latency. In contrast, high levels of ERK1/2 activation at earlier time points and a moderate level of activation at later times were observed. p38 mitogen-activated protein kinase was activated only at later time points, and AKT was activated in a cyclic manner. Studies with UV-inactivated KSHV suggested a role for virus entry stages in NF-κB induction and a requirement for KSHV viral gene expression in sustained induction. Inhibition of NF-κB did not affect target cell entry by KSHV but significantly reduced the expression of viral latent open reading frame 73 and lytic genes. KSHV infection induced the activation of several host transcription factors, including AP-1 family members, as well as several cytokines, growth factors, and angiogenic factors, which were significantly affected by NF-κB inhibition. These results suggest that during de novo infection, KSHV induces sustained levels of NF-κB to regulate viral and host cell genes and thus possibly regulates the establishment of latent infection.

scholarly journals De NovoTranscriptome Assembly and Differential Gene Expression Profiling of ThreeCapra hircusSkin Types during Anagen of the Hair Growth Cycle

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Teng Xu ◽  
Xudong Guo ◽  
Hui Wang ◽  
Xiaoyuan Du ◽  
Xiaoyu Gao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
De Novo ◽  
Growth Cycle ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Differentially Expressed ◽  
Kegg Pathway Database ◽  
Anagen Phase

Despite that goat is one of the best nonmodel systems for villus growth studies and hair biology, limited gene resources associated with skin or hair follicles are available. In the present study, using Illumina/Solexa sequencing technology, wede novoassembled 130 million mRNA-Seq reads into a total of 49,115 contigs. Searching public databases revealed that about 45% of the total contigs can be annotated as known proteins, indicating that some of the assembled contigs may have previously uncharacterized functions. Functional classification by KOG and GO showed that activities associated with metabolism are predominant in goat skin during anagen phase. Many signaling pathways was also created based on the mapping of assembled contigs to the KEGG pathway database, some of which have been previously demonstrated to have diverse roles in hair follicle and hair shaft formation. Furthermore, gene expression profiling of three skin types identified ~6,300 transcript-derived contigs that are differentially expressed. These genes mainly enriched in the functional cluster associated with cell cycle and cell division. The large contig catalogue as well as the genes which were differentially expressed in different skin types provide valuable candidates for further characterization of gene functions.

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