Individually or as a Team—The Immunological Milieu in the Lung Caused by Migrating Single-Sex or Mixed-Sex Larvae of Schistosoma mansoni

Abstract

While the lung is considered an efficient site for stopping the larvae of the acute Schistosoma spp. infection phase from migrating through extensive inflammatory responses in the surrounding tissues, little is known about these processes. To date, the highest resistance to infection has been achieved in experimental studies with radiation-attenuated cercariae immunization, which elicits a strong Th1/Th2 response in the lung and results in up to 80% protection. Based on our own studies demonstrating a systemic, unpolarized Th1/Th2 response resulting from infection with male or female Schistosoma mansoni, we hypothesize that this atypical immune response is already detectable during the pulmonary passage of parasite larvae. Therefore, we examined the immune milieu in the lungs of mice caused by migrating schistosome larvae, either male or female (single-sex groups) or male + female (bisexual control), 4 and 16 days after infection in bronchoalveolar lavage and lung tissue by flow cytometry, qPCR, and multiplex analyzes. Our results show only minor differences in the inflammatory profile between the single-sex groups but significant differences compared with the bisexual control group. Both single-sex infected groups have increased expression of inflammatory markers in lung tissue, higher numbers of cytotoxic T cells (day 4 post-infection) and more T helper cells (day 16 post-infection), compared with the bisexual control group. A single-sex infection, regardless of whether it is an infection with male or female cercariae, causes an immune milieu in the lung that is clearly different from an infection with both sexes. In terms of identifying therapeutic targets to achieve resistance to re-infection, it is of great scientific interest to identify the differences in the inflammatory potential of male or female and male + female parasites.