Local Immune Responses of the Chinese Water Buffalo, Bubalus bubalis, against Schistosoma japonicum Larvae: Crucial Insights for Vaccine Design.

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. Author Summary: Schistosomiasis is caused by a parasitic blood fluke, and in parts of Asia it infects both humans and livestock such as water buffaloes. This makes controlling the disease more difficult, because both humans and livestock must be treated regularly. A vaccine given to buffaloes is likely to reduce human infection rates and improve buffalo health by providing long-lasting protection from re-infection; at present no vaccines are available. Older buffaloes are known to have some immunity to schistosomiasis which is acquired over time; however how this occurs is not understood. In this study we investigated the immune response of buffalo against the schistosome larvae, which are vulnerable to immune attack, and hence are the ideal stage to target for vaccination. We found that the buffalo produces a profound allergic type-2 response as larvae penetrate the skin, with significant cellular infiltrates and abscesses. When the larvae move next to the lungs, a uniquely type-1 response was induced. This skin response is much greater than more susceptible animals such as mice, and may be a mechanism for larval killing in the buffalo. This study offers insight into the immunobiology of an important host for schistosomiasis and may help in designing better vaccines. [ABSTRACT FROM AUTHOR]