Quiescent innate response to infective filariae by human Langerhans’ cells suggests a strategy of immune evasion
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE42694 | GEO | 2012/12/04
SECONDARY ACCESSION(S): PRJNA182745
REPOSITORIES: GEO
Similar Datasets
Project description:Filarial infection is initiated by mosquito-derived, third-stage larvae (L3) deposited on the skin that transits through the epidermis containing Langerhans' cells (LC) and keratinocytes (KC), among other cells. This earliest interaction between L3 and the LC likely conditions the priming of the immune system to the parasite. To determine the nature of this interaction, human LC (Langerin+, E-cadherin+, CD1a+) were generated in vitro and exposed to live L3. LC exposed to live L3 for 48 h showed no alterations in cell surface markers CD14, CD86, CD83, CD207, E-cadherin, CD80, CD40, and HLA-DR or in mRNA expression of inflammation-associated genes such as IL-18, IL-18BP, and caspase 1. In contrast to L3, live tachyzoites of Toxoplasma gondii, an intracellular parasite, induced production of CXCL9, IP 10, and IL-6 in LC. Furthermore, pre-exposure of LC to L3 did not alter TLR3- or TLR4-mediated expression of pro-inflammatory cytokines IL-1β, IFN-γ, IL-6, or IL-10. Interestingly, co-cultures of KC and LC produced significantly more IL-18, IL-1α, and IL-8 than did cultures of LC alone, although exposure of the co-cultures to live L3 did not result in altered cytokine production. Microarray examination of ex vivo LC from skin blisters that were exposed to live L3 also showed few significant changes in gene expression compared with unexposed blisters, further underscoring the relatively muted response of LC to L3. Our data suggest that failure by LC to initiate an inflammatory response to the invasive stage of filarial parasites may be a strategy for immune evasion by the filarial parasite. Skin blisters from 6 healthy volunteers are either cultured in culture media alone as control samples or being exposed to 5 L3s in a transwell in a 24 well tissue culture plates for 48 hours . 12 samples were analyzed in total
2012-12-04 | E-GEOD-42694 | biostudies-arrayexpress
Project description:To understand the genes regulating the molting of L3 to L4 larvae upon induction with ascorbic acid over a 10-day period in a controlled in-vitro molting model of the filarial parasite B.malayi.
2018-03-01 | GSE54203 | GEO
Project description:Filarial nematodes are arthropod-borne nematodes that cause a variety of economically important diseases such as onchocerciasis (river blindness), lymphatic filariasis, and heartworm disease. The most widespread filarial disease of humans is lymphatic filariasis, caused by worms in the genera Wuchereria and Brugia. Lymphatic filariasis is an economic and social burden in endemic countries and affects approximately 119 million people worldwide (Michael, 1997). In humans, the worms live in and block the lymph vessels, causing improper flow of lymph, and inflammation of the lymphatic system. The symptoms are fever, swollen limbs and genitals, generalized malaise, and can progress to a debilitating condition known as elephantiasis This research focuses on the transmission of these worms to the disseminating mosquito host, and it is based on the interesting observation that mf must be at least 7 days old to successfully infect the mosquito (de Hollanda, 1982). Newborn mf that have not âmaturedâ cannot successfully penetrate the midgut of the mosquito, and subsequently cannot develop to the L3 stage (Fuhrman, 1987). Previous work done by another group 20 years ago suggests that the molecular makeup of the worm surface changes during this maturation process (Furman, 1983 a and b). We used microarray analysis to characterize changes in gene expression that take place during the mf maturation process. Understanding the gene expression changes that occur as the mf mature will allow us to understand the nature of the philological transition that allows mf to move from the human to the mosquito host. With this information in hand, we can eventually identify parasite molecules that could be targeted to either stop parasite reproduction or prevent transmission of the mf to the mosquito. This would stop parasite transmission in endemic areas. Two biological replicates were performed each with two technical replicates.
2010-05-22 | E-GEOD-14940 | biostudies-arrayexpress
Project description:Filarial nematodes are arthropod-borne nematodes that cause a variety of economically important diseases such as onchocerciasis (river blindness), lymphatic filariasis, and heartworm disease. The most widespread filarial disease of humans is lymphatic filariasis, caused by worms in the genera Wuchereria and Brugia. Lymphatic filariasis is an economic and social burden in endemic countries and affects approximately 119 million people worldwide (Michael, 1997). In humans, the worms live in and block the lymph vessels, causing improper flow of lymph, and inflammation of the lymphatic system. The symptoms are fever, swollen limbs and genitals, generalized malaise, and can progress to a debilitating condition known as elephantiasis This research focuses on the transmission of these worms to the disseminating mosquito host, and it is based on the interesting observation that mf must be at least 7 days old to successfully infect the mosquito (de Hollanda, 1982). Newborn mf that have not â??maturedâ?? cannot successfully penetrate the midgut of the mosquito, and subsequently cannot develop to the L3 stage (Fuhrman, 1987). Previous work done by another group 20 years ago suggests that the molecular makeup of the worm surface changes during this maturation process (Furman, 1983 a and b). We used microarray analysis to characterize changes in gene expression that take place during the mf maturation process. Understanding the gene expression changes that occur as the mf mature will allow us to understand the nature of the philological transition that allows mf to move from the human to the mosquito host. With this information in hand, we can eventually identify parasite molecules that could be targeted to either stop parasite reproduction or prevent transmission of the mf to the mosquito. This would stop parasite transmission in endemic areas. Brugia pahangi mature mf (30 days and older) RNA was compared to immature mf (3 days and younger). Three biological replicates were performed each with two technical replicates
2010-05-22 | E-GEOD-14939 | biostudies-arrayexpress
Project description:Filarial nematodes are arthropod-borne nematodes that cause a variety of economically important diseases such as onchocerciasis (river blindness), lymphatic filariasis, and heartworm disease. The most widespread filarial disease of humans is lymphatic filariasis, caused by worms in the genera Wuchereria and Brugia. Lymphatic filariasis is an economic and social burden in endemic countries and affects approximately 119 million people worldwide (Michael, 1997). In humans, the worms live in and block the lymph vessels, causing improper flow of lymph, and inflammation of the lymphatic system. The symptoms are fever, swollen limbs and genitals, generalized malaise, and can progress to a debilitating condition known as elephantiasis This research focuses on the transmission of these worms to the disseminating mosquito host, and it is based on the interesting observation that mf must be at least 7 days old to successfully infect the mosquito (de Hollanda, 1982). Newborn mf that have not â??maturedâ?? cannot successfully penetrate the midgut of the mosquito, and subsequently cannot develop to the L3 stage (Fuhrman, 1987). Previous work done by another group 20 years ago suggests that the molecular makeup of the worm surface changes during this maturation process (Furman, 1983 a and b). We used microarray analysis to characterize changes in gene expression that take place during the mf maturation process. Understanding the gene expression changes that occur as the mf mature will allow us to understand the nature of the philological transition that allows mf to move from the human to the mosquito host. With this information in hand, we can eventually identify parasite molecules that could be targeted to either stop parasite reproduction or prevent transmission of the mf to the mosquito. This would stop parasite transmission in endemic areas. This SuperSeries is composed of the following subset Series: GSE14939: Brugia pahangi mature vs immature microfilariae GSE14940: Brugia malayi mature vs immature microfilariae Refer to individual Series
2009-10-01 | E-GEOD-15017 | biostudies-arrayexpress
Project description:Filarial nematodes are arthropod-borne nematodes that cause a variety of economically important diseases such as onchocerciasis (river blindness), lymphatic filariasis, and heartworm disease. The most widespread filarial disease of humans is lymphatic filariasis, caused by worms in the genera Wuchereria and Brugia. Lymphatic filariasis is an economic and social burden in endemic countries and affects approximately 119 million people worldwide (Michael, 1997). In humans, the worms live in and block the lymph vessels, causing improper flow of lymph, and inflammation of the lymphatic system. The symptoms are fever, swollen limbs and genitals, generalized malaise, and can progress to a debilitating condition known as elephantiasis This research focuses on the transmission of these worms to the disseminating mosquito host, and it is based on the interesting observation that mf must be at least 7 days old to successfully infect the mosquito (de Hollanda, 1982). Newborn mf that have not ‘matured’ cannot successfully penetrate the midgut of the mosquito, and subsequently cannot develop to the L3 stage (Fuhrman, 1987). Previous work done by another group 20 years ago suggests that the molecular makeup of the worm surface changes during this maturation process (Furman, 1983 a and b). We used microarray analysis to characterize changes in gene expression that take place during the mf maturation process. Understanding the gene expression changes that occur as the mf mature will allow us to understand the nature of the philological transition that allows mf to move from the human to the mosquito host. With this information in hand, we can eventually identify parasite molecules that could be targeted to either stop parasite reproduction or prevent transmission of the mf to the mosquito. This would stop parasite transmission in endemic areas. This SuperSeries is composed of the SubSeries listed below.
2009-10-01 | GSE15017 | GEO
Project description:Filarial nematodes are arthropod-borne nematodes that cause a variety of economically important diseases such as onchocerciasis (river blindness), lymphatic filariasis, and heartworm disease. The most widespread filarial disease of humans is lymphatic filariasis, caused by worms in the genera Wuchereria and Brugia. Lymphatic filariasis is an economic and social burden in endemic countries and affects approximately 119 million people worldwide (Michael, 1997). In humans, the worms live in and block the lymph vessels, causing improper flow of lymph, and inflammation of the lymphatic system. The symptoms are fever, swollen limbs and genitals, generalized malaise, and can progress to a debilitating condition known as elephantiasis This research focuses on the transmission of these worms to the disseminating mosquito host, and it is based on the interesting observation that mf must be at least 7 days old to successfully infect the mosquito (de Hollanda, 1982). Newborn mf that have not ‘matured’ cannot successfully penetrate the midgut of the mosquito, and subsequently cannot develop to the L3 stage (Fuhrman, 1987). Previous work done by another group 20 years ago suggests that the molecular makeup of the worm surface changes during this maturation process (Furman, 1983 a and b). We used microarray analysis to characterize changes in gene expression that take place during the mf maturation process. Understanding the gene expression changes that occur as the mf mature will allow us to understand the nature of the philological transition that allows mf to move from the human to the mosquito host. With this information in hand, we can eventually identify parasite molecules that could be targeted to either stop parasite reproduction or prevent transmission of the mf to the mosquito. This would stop parasite transmission in endemic areas.
2009-10-01 | GSE14940 | GEO
Project description:Filarial nematodes are arthropod-borne nematodes that cause a variety of economically important diseases such as onchocerciasis (river blindness), lymphatic filariasis, and heartworm disease. The most widespread filarial disease of humans is lymphatic filariasis, caused by worms in the genera Wuchereria and Brugia. Lymphatic filariasis is an economic and social burden in endemic countries and affects approximately 119 million people worldwide (Michael, 1997). In humans, the worms live in and block the lymph vessels, causing improper flow of lymph, and inflammation of the lymphatic system. The symptoms are fever, swollen limbs and genitals, generalized malaise, and can progress to a debilitating condition known as elephantiasis This research focuses on the transmission of these worms to the disseminating mosquito host, and it is based on the interesting observation that mf must be at least 7 days old to successfully infect the mosquito (de Hollanda, 1982). Newborn mf that have not ‘matured’ cannot successfully penetrate the midgut of the mosquito, and subsequently cannot develop to the L3 stage (Fuhrman, 1987). Previous work done by another group 20 years ago suggests that the molecular makeup of the worm surface changes during this maturation process (Furman, 1983 a and b). We used microarray analysis to characterize changes in gene expression that take place during the mf maturation process. Understanding the gene expression changes that occur as the mf mature will allow us to understand the nature of the philological transition that allows mf to move from the human to the mosquito host. With this information in hand, we can eventually identify parasite molecules that could be targeted to either stop parasite reproduction or prevent transmission of the mf to the mosquito. This would stop parasite transmission in endemic areas.
2009-10-01 | GSE14939 | GEO
Project description:The zoonotic mosquito-borne filarial nematode Dirofilaria repens causes subcutaneous and ocular infections in dogs, cats and humans. Microfilariae (mf) are taken up by mosquitoes from infected vertebrate hosts which develop in the mosquito to the infectious third stage larvae (L3). These are transmitted to new vertebrate hosts and develop over two further moults to adult worms. The aims of the project were 1) the de novo sequencing and annotation of the D. repens genome and 2) comparative transcriptome analyses of the developmental stages mf and L3 as we hypothesized remarkable differences in gene expression between the different developmental stages. Genomic DNA was obtained from adult male D. repens. RNA was extracted from microfilariae from naturally infected dogs and from L3 produced in Aedes aegypti mosquitoes fed on blood spiked with microfi-lariae. The 99.59 MB genome was around 17% larger than that of the related species D. immitis (dog heartworm) and contained 8.9% fewer predicted genes (10,357). Around 1.8% of identified proteins (206/11,262) could not be mapped to D. immitis. Out of these, 6 (2.9 %) presented an ortholog in all other considered filarial nematodes (e.g. Loa loa) and Caenorhabditis elegans. A sig-nificantly higher number of D. repens proteins as compared to D. immitis mapped to the filarial nem-atode L. loa, reflecting the similarity in biology of D. repens and L. loa. A total of 876 genes were differentially expressed, of which 591 could be annotated in UniProtKB/Swiss-Prot. In particular, 155 genes with a UniProtKB/Swiss-Prot annotation to C. elegans and filarial nematodes were upregulat-ed in the L3 and 57 in the mf stage, respectively. Fifteen GO BP (Gene Ontology Biological Pro-cesses) were significantly enriched for the L3 group and 12 for the mf. These data provide first in-sight into the differential gene expression profiles of this filarial nematode and can serve for future investigations of metabolic processes and stage-specific diagnostics.
2020-01-01 | GSE128572 | GEO
Project description:Transcriptional profiling of adult males and females of the lymphatic dwelling filarial parasite Brugia malayi Keywords: Gender based transcripts, filaria
2010-12-30 | GSE12944 | GEO