Local immune responses of the Chinese water buffalo, Bubalus bubalis, against Schistosoma japonicum larvae: crucial insights for vaccine design
- McWilliam, Hamish, Piedrafita, David, Li, Yuesheng, Zheng, Mao, He, Yongkang, Yu, Xinling, McManus, Donald, Meeusen, Els
- Authors: McWilliam, Hamish , Piedrafita, David , Li, Yuesheng , Zheng, Mao , He, Yongkang , Yu, Xinling , McManus, Donald , Meeusen, Els
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS Neglected Tropical Diseases. Vol.7, no.9(Art.No: e2460) (2013), p. 1-11
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- Description: Asian schistosomiasis is a zoonotic parasitic disease infecting up to a million people and threatening tens of millions more. Control of this disease is hindered by the animal reservoirs of the parasite, in particular the water buffalo (Bubalus bubalis), which is responsible for significant levels of human transmission. A transmission-blocking vaccine administered to buffaloes is a realistic option which would aid in the control of schistosomiasis. This will however require a better understanding of the immunobiology of schistosomiasis in naturally exposed buffaloes, particularly the immune response to migrating schistosome larvae, which are the likely targets of an anti-schistosome vaccine. To address this need we investigated the immune response at the major sites of larval migration, the skin and the lungs, in previously exposed and re-challenged water buffaloes. In the skin, a strong allergic-type inflammatory response occurred, characterised by leukocyte and eosinophil infiltration including the formation of granulocytic abscesses. Additionally at the local skin site, interleukin-5 transcript levels were elevated, while interleukin-10 levels decreased. In the skin-draining lymph node (LN) a predominant type-2 profile was seen in stimulated cells, while in contrast a type-1 profile was detected in the lung draining LN, and these responses occurred consecutively, reflecting the timing of parasite migration. The intense type-2 immune response at the site of cercarial penetration is significantly different to that seen in naive and permissive animal models such as mice, and suggests a possible mechanism for immunity. Preliminary data also suggest a reduced and delayed immune response occurred in buffaloes given high cercarial challenge doses compared with moderate infections, particularly in the skin. This study offers a deeper understanding into the immunobiology of schistosomiasis in a natural host, which may aid in the future design of more effective vaccines.
- Authors: McWilliam, Hamish , Piedrafita, David , Li, Yuesheng , Zheng, Mao , He, Yongkang , Yu, Xinling , McManus, Donald , Meeusen, Els
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS Neglected Tropical Diseases. Vol.7, no.9(Art.No: e2460) (2013), p. 1-11
- Full Text:
- Reviewed:
- Description: Asian schistosomiasis is a zoonotic parasitic disease infecting up to a million people and threatening tens of millions more. Control of this disease is hindered by the animal reservoirs of the parasite, in particular the water buffalo (Bubalus bubalis), which is responsible for significant levels of human transmission. A transmission-blocking vaccine administered to buffaloes is a realistic option which would aid in the control of schistosomiasis. This will however require a better understanding of the immunobiology of schistosomiasis in naturally exposed buffaloes, particularly the immune response to migrating schistosome larvae, which are the likely targets of an anti-schistosome vaccine. To address this need we investigated the immune response at the major sites of larval migration, the skin and the lungs, in previously exposed and re-challenged water buffaloes. In the skin, a strong allergic-type inflammatory response occurred, characterised by leukocyte and eosinophil infiltration including the formation of granulocytic abscesses. Additionally at the local skin site, interleukin-5 transcript levels were elevated, while interleukin-10 levels decreased. In the skin-draining lymph node (LN) a predominant type-2 profile was seen in stimulated cells, while in contrast a type-1 profile was detected in the lung draining LN, and these responses occurred consecutively, reflecting the timing of parasite migration. The intense type-2 immune response at the site of cercarial penetration is significantly different to that seen in naive and permissive animal models such as mice, and suggests a possible mechanism for immunity. Preliminary data also suggest a reduced and delayed immune response occurred in buffaloes given high cercarial challenge doses compared with moderate infections, particularly in the skin. This study offers a deeper understanding into the immunobiology of schistosomiasis in a natural host, which may aid in the future design of more effective vaccines.
Generation of a Novel Bacteriophage Library displaying scFv antibody fragments from the natural Buffalo host to identify antigens from adult Schistosoma japonicum for diagnostic development
- Hosking, Christopher, McWilliam, Hamish, Driguez, Patrick, Piedrafita, David, Li, Yuesheng, McManus, Donald, Ilag, Leodevico, Meeusen, Els, De Veer, Michael
- Authors: Hosking, Christopher , McWilliam, Hamish , Driguez, Patrick , Piedrafita, David , Li, Yuesheng , McManus, Donald , Ilag, Leodevico , Meeusen, Els , De Veer, Michael
- Date: 2015
- Type: Text , Journal article
- Relation: PLoS Neglected Tropical Diseases Vol. 9, no. 12 (2015), p. 1-20
- Full Text:
- Reviewed:
- Description: The development of effective diagnostic tools will be essential in the continuing fight to reduce schistosome infection; however, the diagnostic tests available to date are generally laborious and difficult to implement in current parasite control strategies. We generated a series of single-chain antibody Fv domain (scFv) phage display libraries from the portal lymph node of field exposed water buffaloes, Bubalus bubalis, 11–12 days post challenge with Schistosoma japonicum cercariae. The selected scFv-phages showed clear enrichment towards adult schistosomes and excretory-secretory (ES) proteins by immunofluorescence, ELISA and western blot analysis. The enriched libraries were used to probe a schistosome specific protein microarray resulting in the recognition of a number of proteins, five of which were specific to schistosomes, with RNA expression predominantly in the adult life-stage based on interrogation of schistosome expressed sequence tags (EST). As the libraries were enriched by panning against ES products, these antigens may be excreted or secreted into the host vasculature and hence may make good targets for a diagnostic assay. Further selection of the scFv library against infected mouse sera identified five soluble scFv clones that could selectively recognise soluble whole adult preparations (SWAP) relative to an irrelevant protein control (ovalbumin). Furthermore, two of the identified scFv clones also selectively recognised SWAP proteins when spiked into naïve mouse sera. These host B-cell derived scFvs that specifically bind to schistosome protein preparations will be valuable reagents for further development of a cost effective point-of-care diagnostic test. © 2015 Hosking et al.
- Authors: Hosking, Christopher , McWilliam, Hamish , Driguez, Patrick , Piedrafita, David , Li, Yuesheng , McManus, Donald , Ilag, Leodevico , Meeusen, Els , De Veer, Michael
- Date: 2015
- Type: Text , Journal article
- Relation: PLoS Neglected Tropical Diseases Vol. 9, no. 12 (2015), p. 1-20
- Full Text:
- Reviewed:
- Description: The development of effective diagnostic tools will be essential in the continuing fight to reduce schistosome infection; however, the diagnostic tests available to date are generally laborious and difficult to implement in current parasite control strategies. We generated a series of single-chain antibody Fv domain (scFv) phage display libraries from the portal lymph node of field exposed water buffaloes, Bubalus bubalis, 11–12 days post challenge with Schistosoma japonicum cercariae. The selected scFv-phages showed clear enrichment towards adult schistosomes and excretory-secretory (ES) proteins by immunofluorescence, ELISA and western blot analysis. The enriched libraries were used to probe a schistosome specific protein microarray resulting in the recognition of a number of proteins, five of which were specific to schistosomes, with RNA expression predominantly in the adult life-stage based on interrogation of schistosome expressed sequence tags (EST). As the libraries were enriched by panning against ES products, these antigens may be excreted or secreted into the host vasculature and hence may make good targets for a diagnostic assay. Further selection of the scFv library against infected mouse sera identified five soluble scFv clones that could selectively recognise soluble whole adult preparations (SWAP) relative to an irrelevant protein control (ovalbumin). Furthermore, two of the identified scFv clones also selectively recognised SWAP proteins when spiked into naïve mouse sera. These host B-cell derived scFvs that specifically bind to schistosome protein preparations will be valuable reagents for further development of a cost effective point-of-care diagnostic test. © 2015 Hosking et al.
The oligomeric assembly of galectin-11 is critical for anti-parasitic activity in sheep (Ovis aries)
- Sakthivel, Dhanasekaran, Preston, Sarah, Gasser, Robin, Meeusen, Els, Piedrafita, David
- Authors: Sakthivel, Dhanasekaran , Preston, Sarah , Gasser, Robin , Meeusen, Els , Piedrafita, David
- Date: 2020
- Type: Text , Journal article
- Relation: Communications Biology Vol. 3, no. 1 (2020), p.
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- Description: Galectins are a family of glycan-binding molecules with a characteristic affinity for ß-D-glycosides that mediate a variety of important cellular functions, including immune and inflammatory responses. Galectin-11 (LGALS-11) has been recently identified as a mediator induced specifically in animals against gastrointestinal nematodes and can interfere with parasite growth and development. Here, we report that at least two natural genetic variants of LGALS-11 exist in sheep, and demonstrate fundamental differences in anti-parasitic activity, correlated with their ability to dimerise. This study improves our understanding of the role of galectins in the host immune and inflammatory responses against parasitic nematodes and provides a basis for genetic studies toward selective breeding of animals for resistance to parasites. © 2020, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Dhanasekaran Sakthivel, Sarah Preston, Robin Gasser, Els Meeusen, David Piedrafita” is provided in this record**
The oligomeric assembly of galectin-11 is critical for anti-parasitic activity in sheep (Ovis aries)
- Authors: Sakthivel, Dhanasekaran , Preston, Sarah , Gasser, Robin , Meeusen, Els , Piedrafita, David
- Date: 2020
- Type: Text , Journal article
- Relation: Communications Biology Vol. 3, no. 1 (2020), p.
- Full Text:
- Reviewed:
- Description: Galectins are a family of glycan-binding molecules with a characteristic affinity for ß-D-glycosides that mediate a variety of important cellular functions, including immune and inflammatory responses. Galectin-11 (LGALS-11) has been recently identified as a mediator induced specifically in animals against gastrointestinal nematodes and can interfere with parasite growth and development. Here, we report that at least two natural genetic variants of LGALS-11 exist in sheep, and demonstrate fundamental differences in anti-parasitic activity, correlated with their ability to dimerise. This study improves our understanding of the role of galectins in the host immune and inflammatory responses against parasitic nematodes and provides a basis for genetic studies toward selective breeding of animals for resistance to parasites. © 2020, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Dhanasekaran Sakthivel, Sarah Preston, Robin Gasser, Els Meeusen, David Piedrafita” is provided in this record**
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