Liver-dependent protective immune responses against Ascaris infections

Abstract text

Introduction: The liver is an effected organ of different parasites whether it is protozoan or helminth infections. Even so for both human and porcine Ascaris infections, which affect > 0.7 billion humans in the global south and lead to huge economic losses in the pig farming, respectively. In fact, larval stages of Ascaris when migrating through the liver are taking advantage of the tolerogenic environment hepatic tissue provides. However, concomitantly, the formation of pathological lesions in the liver, known as white spots, also suggests a strong liver immune response and inflammation lead to elimination of the parasites during the initial phase of larval migration.Objectives: In this research project, we aim to determine whether resistance to Ascaris larval migration occurs in the liver and whether liver innate immune cells are involved in the elimination of Ascaris larvae or are targets of immunoregulation by the parasite.Materials & methods: To address this, we infected two different mouse strains with Ascaris that mimic hepato-tracheal migration of natural hosts but show contrasting susceptibilities to Ascaris infection. We immunologically analyzed liver innate immune cells such as innate lymphocytes, eosinophils, neutrophils and macrophages (MO) to determine their composition and phenotype during liver and lung stage of an Ascaris infection.Results: Our results show, resistant CBA mice harbor significantly less Ascaris suum larvae in the liver during liver stage of infection compared to susceptible C57BL/6 mice. Interestingly, hepatic resistance against Ascaris larval migration was associated with differences in polarization of liver MO. Already intrinsically, the frequencies of alternatively activated MO were elevated in the liver of the resistant strain in comparison to susceptible strain. Interestingly, Ascaris infection led to a hepatic downregulation of this host protective M2 macrophage response. Simultaneously, both mouse strains showed increased iNOS expression in liver MO which suggest larval clearance might be partly associated with a type 1 response but not being an effective host protective response as in the susceptible strain significant amounts of larvae were detectable despite iNOS production.Conclusion: Alternative activation of MO in liver seems to be associated with resistance and being actively counterregulated by infection. In contrast, iNOS production of liver macrophages is induced but ineffective in Ascaris larval killing.