Children's National Health System Posters

Title

Exposure to Early Life Cycle Stages of Schistosoma haematobium Infection Influences Subsequent Immune Responses to Eggs

Poster Number

353

Document Type

Poster

Status

Postdoc

Abstract Category

Immunology/Infectious Diseases

Keywords

Schistosomiasis, NTD, Immunology, Parasitology ,Urology

Publication Date

Spring 2018

Abstract

Urogenital schistosomiasis causes bladder dysfunction, hematuria, fibrosis, and urothelial changes that could lead to carcinogenesis. Exposure to schistosome infested waters, a major concern particularly for school-aged children, can lead to loss of productive life years due to heavy morbidity. Heavy morbidity contributes to the vicious cycle whereby schistosomiasis is the cause as well as the effect of poverty. Despite the global impact of urogenital schistosomiasis, relatively little is known about the mechanisms that lead to its pathophysiology. This is primarily due to the lack of an experimentally tractable animal model – rodent models of urogenital schistosomiasis result in little to no involvement of the urogenital system, thus failing to recapitulate the human disease. Hence, we sought to develop a mouse model of urogenital schistosomiasis that bypasses critical weaknesses of current models, specifically, to study the effect of prior cercarial-, schistosomular-, and worm-triggered immune responses on the subsequent egg-induced granulomatous reaction. 4 groups of BALB/c mice underwent the following treatments: 1) bladder wall injection with vehicle alone; 2) bladder wall injection with 3000 S. haematobium eggs; 3) percutaneous infection with 150 S. haematobium cercariae via tail immersion and bladder wall injection with vehicle; and 4) both percutaneous infection and egg bladder wall injection. Briefly, mice were infected at week 0. At week 5, mice underwent bladder wall injections. Mice were sacrificed at week 8 to collect bladder specimen for cytokine analysis. Sera were collected one day prior to sacrifice for cytokine analysis. A distinct immune response was observed from mice receiving bladder wall injection with viable eggs following percutaneous infection compared to mice that received egg bladder wall injection without cercarial exposure. We were able to reproduce fundamental immunological aspects of human urogenital schistosomiasis, such as a collective type 2 inflammatory response in the bladder and sera of egg-injected, cercaria-exposed animals compared to vehicle injected, cercaria unexposed animals. Furthermore, we observed Th0 and Th1 responses in egg-injected, cercaria-exposed animals, possibly attributed to exposure to cercariae, schistosomula, and/or adult worms, thus highlighting an important advantage to the combined model for understanding systemic immune responses to S. haematobium. Development of the proposed model herein can lead to better tools for progress on therapeutics or vaccines for this neglected global health problem.

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Exposure to Early Life Cycle Stages of Schistosoma haematobium Infection Influences Subsequent Immune Responses to Eggs

Urogenital schistosomiasis causes bladder dysfunction, hematuria, fibrosis, and urothelial changes that could lead to carcinogenesis. Exposure to schistosome infested waters, a major concern particularly for school-aged children, can lead to loss of productive life years due to heavy morbidity. Heavy morbidity contributes to the vicious cycle whereby schistosomiasis is the cause as well as the effect of poverty. Despite the global impact of urogenital schistosomiasis, relatively little is known about the mechanisms that lead to its pathophysiology. This is primarily due to the lack of an experimentally tractable animal model – rodent models of urogenital schistosomiasis result in little to no involvement of the urogenital system, thus failing to recapitulate the human disease. Hence, we sought to develop a mouse model of urogenital schistosomiasis that bypasses critical weaknesses of current models, specifically, to study the effect of prior cercarial-, schistosomular-, and worm-triggered immune responses on the subsequent egg-induced granulomatous reaction. 4 groups of BALB/c mice underwent the following treatments: 1) bladder wall injection with vehicle alone; 2) bladder wall injection with 3000 S. haematobium eggs; 3) percutaneous infection with 150 S. haematobium cercariae via tail immersion and bladder wall injection with vehicle; and 4) both percutaneous infection and egg bladder wall injection. Briefly, mice were infected at week 0. At week 5, mice underwent bladder wall injections. Mice were sacrificed at week 8 to collect bladder specimen for cytokine analysis. Sera were collected one day prior to sacrifice for cytokine analysis. A distinct immune response was observed from mice receiving bladder wall injection with viable eggs following percutaneous infection compared to mice that received egg bladder wall injection without cercarial exposure. We were able to reproduce fundamental immunological aspects of human urogenital schistosomiasis, such as a collective type 2 inflammatory response in the bladder and sera of egg-injected, cercaria-exposed animals compared to vehicle injected, cercaria unexposed animals. Furthermore, we observed Th0 and Th1 responses in egg-injected, cercaria-exposed animals, possibly attributed to exposure to cercariae, schistosomula, and/or adult worms, thus highlighting an important advantage to the combined model for understanding systemic immune responses to S. haematobium. Development of the proposed model herein can lead to better tools for progress on therapeutics or vaccines for this neglected global health problem.