Abstract
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.
Highlights
Asian schistosomiasis, caused by Schistosoma japonicum, is a parasitic disease endemic in the marsh and lake regions of China, along the Yangtze River basin and mountainous regions [1,2], and parts of the Philippines and Indonesia [3]
Schistosomiasis is caused by a parasitic blood fluke, and in parts of Asia it infects both humans and livestock such as water buffaloes
In this study we investigated the immune response of buffalo against the schistosome larvae, which are vulnerable to immune attack, and are the ideal stage to target for vaccination
Summary
Asian schistosomiasis, caused by Schistosoma japonicum, is a parasitic disease endemic in the marsh and lake regions of China, along the Yangtze River basin and mountainous regions [1,2], and parts of the Philippines and Indonesia [3]. The domestic water buffalo, Bubalus bubalis, is considered the most significant animal reservoir of schistosomiasis in China [1,9,10] where it has been shown to account for up to 75% of human transmission [11]. This results in the need for routine PZQ treatment of livestock in addition to humans for parasite control [1]. An effective vaccine for buffalo alone would significantly reduce human morbidity as well as improve buffalo health [19], and for this reason an effort has been made to develop a transmissionblocking veterinary vaccine [17]
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