Schistosomes in the Lung: Immunobiology and Opportunity

Abstract

Schistosome infection is a major cause of global morbidity, particularly in sub-Saharan Africa. However, there is no effective vaccine for this major neglected tropical disease, and re-infection routinely occurs after chemotherapeutic treatment. Following invasion through the skin, larval schistosomula enter the circulatory system and migrate through the lung before maturing to adulthood in the mesenteric or urogenital vasculature. Eggs released from adult worms can become trapped in various tissues, with resultant inflammatory responses leading to hepato-splenic, intestinal, or urogenital disease – processes that have been extensively studied in recent years. In contrast, although lung pathology can occur in both the acute and chronic phases of schistosomiasis, the mechanisms underlying pulmonary disease are particularly poorly understood. In chronic infection, egg-mediated fibrosis and vascular destruction can lead to the formation of portosystemic shunts through which eggs can embolise to the lungs, where they can trigger granulomatous disease. Acute schistosomiasis, or Katayama syndrome, which is primarily evident in non-endemic individuals, occurs during pulmonary larval migration, maturation, and initial egg-production, often involving fever and a cough with an accompanying immune cell infiltrate into the lung. Importantly, lung migrating larvae are not just a cause of inflammation and pathology but are a key target for future vaccine design. However, vaccine efforts are hindered by a limited understanding of what constitutes a protective immune response to larvae. In this review, we explore the current understanding of pulmonary immune responses and inflammatory pathology in schistosomiasis, highlighting important unanswered questions and areas for future research.

Parasitic lung diseases

“…Acute schistosomiasis (Katayama fever) usually occurs among nonimmune travellers and is associated with fever, malaise, fatigue, headache, cough, abdominal pain and urticarial rash [ 29 , 30 ]. The disease is related to the migration, maturation and egg-production of schistosomal larva [ 31 ], and subsequent immunological reactions [ 31 ].…”

Dynamics of host immune response development during Schistosoma mansoni infection

“…Schistosomiasis has a distinctive triphasic immune profile that reflects transformative events within the parasite lifecycle ( 2 ). In brief, the host first progresses through a (pre-patent) acute phase (0-5 WPI; wks post infection), where it responds to immature, lung migrating schistosomula and developing worm pairs ( 3 ). In the second (post-patent) acute phase (5-12 WPI), the host is confronted daily with hundreds of highly immunogenic eggs, and must contend with accompanying inflammation and associated tissue damage ( 4 ).…”

TLR7 controls myeloid-derived suppressor cells expansion and function in the lung of C57BL6 mice infected with Schistosoma japonicum

“…Moreover, the mechanism of immune response induced by S. japonicum is very complex: non-specific immunity and specific immunity are mutually conditional and complementary; humoral and cellular immunity regulate and balance each other; interaction between schistosoma antigens and host MHC; a variety of immune cells, including macrophages, NK cells, B cells and T cells, are involved in the pulmonary lesions in schistosomiasis, and these factors may affect the pathogenesis of schistosomiasis [49][50][51]. Therefore, in the lungs of infected mice, TLR7-KO may affect the immune response of other immune cells, such as B cells and NK cells, and jointly affect the pulmonary lesions of infected mice [26,33].…”