Immune Evasion Strategies of Schistosomes

Abstract

Human schistosomes combat the unique immune systems of two vastly different hosts during their indirect life cycles. In gastropod molluscs, they face a potent innate immune response composed of variable immune recognition molecules and highly phagocytic hemocytes. In humans, a wide variety of innate and adaptive immune processes exist in proximity to these parasites throughout their lifespan. To survive and thrive as the second most common parasitic disease in humans, schistosomes have evolved many techniques to avoid and combat these targeted host responses. Among these techniques are molecular mimicry of host antigens, the utilization of an immune resistant outer tegument, the secretion of several potent proteases, and targeted release of specific immunomodulatory factors affecting immune cell functions. This review seeks to describe these key immune evasion mechanisms, among others, which schistosomes use to survive in both of their hosts. After diving into foundational observational studies of the processes mediating the establishment of schistosome infections, more recent transcriptomic and proteomic studies revealing crucial components of the host/parasite molecular interface are discussed. In order to combat this debilitating and lethal disease, a comprehensive understanding of schistosome immune evasion strategies is necessary for the development of novel therapeutics and treatment plans, necessitating the discussion of the numerous ways in which these parasitic flatworms overcome the immune responses of both hosts.

Experimental infection with Schistosoma mansoni isolated from the wild rodent Holochilus sciureus shows a low parasite burden but induces high schistosomiasis severity in BALB/c mice

“…As mentioned, the infectivity and fecundity rate of S. mansoni would be influenced by the host's immune response, a determinant factor in the host–parasite interaction (McManus et al , 2018; Angeles et al , 2020; Hambrook and Hanington, 2021). Moreover, the type and intensity of the immune response produced by vertebrate hosts are also essential for understanding the development of morbidity associated with schistosomiasis (Pearce and Macdonald, 2002; Abath et al , 2006).…”

Blocking prostanoid receptors switches on multiple immune responses and cascades of inflammatory signaling against larval stages in snail fever

“…On the contrary, poorly immune IFN- γ R −/− mice with a Th2 bias comprised numerous eosinophils and lymphocytes in their pulmonary infiltrate, with large, diffuse foci that were loosely constituted and ineffective in trapping schistosomulae (Molehin et al 2016 ). The extent of IFN- γ release determines the level to which CD4 + effector T-cells group into compact foci, maximizing their ability to trap migrating schistosomulae (Angeles et al 2020 ; Hambrook and Hanington 2021 ). One obvious action of IFN- γ is the activation of macrophages for cytotoxic killing.…”

“…Furthermore, the function of IFN-alpha in lung responses is to activate intercellular adhesion between leukocytes that are the target of the effector (Gomez et al 2015 ). Indeed, alveolar macrophages are the first line of protection against pathogenic organisms in the lung and can induce cytokine overabundance, including chemokinesis (monocyte chemo-attractant protein-1 (MCP-1), macrophage inflammatory protein-1a (MIP-1 α )), pro-inflammatory cytokines (IL-1, IL-6, and TNF- α ) and immune-regulatory cytokines (IL-10, IL-12) (Angeles et al 2020 , Costain et al 2018 , Hambrook and Hanington 2021 ).…”

cGAS exacerbates Schistosoma japonicum infection in a STING-type I IFN-dependent and independent manner

“…The schistosomiasis pandemic in China is caused by infection with Schistosoma japonicum [ 3 ]. A pathological hallmark of schistosomiasis is the formation of granulomas and fibrosis in response to the deposition of eggs [ 4 ]. The innate immune system is critical for the discriminative recognition of self and non-self components.…”