Adults from Kisumu, Kenya have robust γδ T cell responses to Schistosoma mansoni, which are modulated by tuberculosis.

Schistosoma mansoni(SM) is a parasitic helminth that infects over 200 million people and causes severe morbidity. It undergoes a multi-stage life cycle in human hosts and as such stimulates a stage-specific immune response. The human T cell response to SM is complex and varies throughout the life cycle of SM. Relative to the wealth of information regarding the immune response to SM eggs, little is known about the immune response to the adult worm. In addition, while a great deal of research has uncovered mechanisms by which co-infection with helminths modulates immunity to other pathogens, there is a paucity of data on the effect of pathogens on immunity to helminths. As such, we sought to characterize the breadth of the T cell response to SM and determine whether co-infection withMycobacterium tuberculosis(Mtb) modifies SM-specific T cell responses in a cohort of HIV-uninfected adults in Kisumu, Kenya. SM-infected individuals were categorized into three groups by Mtb infection status: active TB (TB), Interferon-gamma Release Assay positive (IGRA+), and Interferon-gamma Release Assay negative (IGRA-). U.S. adults that were seronegative for SM antibodies served as naive controls. We utilized flow cytometry to characterize the T cell repertoire to SM egg and worm antigens. We found that T cells had significantly higher proliferation and cytokine production in response to worm antigen than to egg antigen. The T cell response to SM was dominated by gamma delta T cells that produced TNF alpha and IFN gamma. Furthermore, we found that in individuals infected with Mtb, gamma delta T cells proliferated less in response to SM worm antigens and had higher IL-4 production compared to naive controls. Together these data demonstrate that gamma delta T cells respond robustly to SM worm antigens and that Mtb infection modifies the gamma delta T cell response to SM. Author summary Schistosomiasis, a disease caused by parasitic helminths includingSchistosoma mansoni(SM), affects hundreds of millions of people globally. SM undergoes a complex life cycle within humans resulting in adult worm pairs that release eggs into the circulatory system. The human immune response to SM, especially to adult worms, is not well characterized. In addition, the impact of co-infections, which are common in SM endemic regions, on the immune response to SM is unknown. In this study, we first sought to characterize the T cell response to different stages of the SM life cycle. We next evaluated whether T cell responses to SM were altered in the setting of co-infection withMycobacterium tuberculosis, the bacteria that causes tuberculosis. We determined that human T cell responses to SM adult worm antigen are more robust than to SM egg antigen. This response is dominated by a non-classical T cell subset of gamma delta T cells producing IFN gamma and TNF alpha. Lastly, we found that the ability of gamma delta T cells to proliferate in response to SM worm was lower in individuals with tuberculosis compared to naive controls. This study provides novel insights into the immune response to SM and how tuberculosis may impair SM immunity.