From first contact to challenge: Lung immune modulation by single-sex Schistosoma mansoni infections
- 1Department of Internal Medicine, Division of Infectious Diseases, Nephrology, Endocrinology and Tropical Medicine, Rostock University Medical Center, Rostock, Germany
Abstract
Background: Schistosomiasis is a chronic parasitic disease caused by blood flukes of the genus Schistosoma and remains a major public health concern in endemic regions. Following skin penetration, schistosomula migrate through multiple host tissues before maturing into adult worm within the mesenteric vasculature. Immunological priming critically influences host responses during secondary infections, yet the importance of prior single-sex Schistosoma mansoni infection on pulmonary recall immunity remains largely unknown. Since the lungs serve as an important immunological checkpoint during schistosomula migration, we herein investigated how single-sex and bisexual priming influence the pulmonary immune landscape upon reinfection. Methodology: Using a murine reinfection model, mice were infected with male, female or mixed-sex S. mansoni cercariae and subsequently challenged with a bisexual infection. Pulmonary immune responses were analyzed by expression of key-regulatory genes, high-dimensional flow cytometry, tSNE/FlowSOM clustering and immune cell phenotyping. Conclusions: Single-sex priming resulted in distinct immune responses compared to bisexual infection. Male priming was associated with reduced pulmonary worm burden and a preferential enrichment of circulating CD4+ central and effector memory T cells, whereas female priming promoted the accumulation of CD4+ resident memory T cells together with broader alterations in pulmonary myeloid cell populations. Our findings demonstrate that the sex of primary Schistosoma mansoni infection differently programs pulmonary immune recall responses, particularly through distinct organization of the CD4+ memory T cell compartment. The association between male priming, enrichment of circulating memory T cell subsets and reduced pulmonary worm burden identifies pulmonary memory T cell organization as a potential correlate of protection during reinfection. Author summary: The present study demonstrated that single-sex Schistosoma mansoni priming profoundly shapes the pulmonary immune response upon subsequent bisexual challenge infection. Building upon previous observations that single-sex infections differently affect hepatic pathology, we investigated whether these priming effects are already detectable during the critical pulmonary migration phase of reinfection.
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BibTeX
@article{bischofsberger2026from,
title = {{From first contact to challenge: Lung immune modulation by single-sex Schistosoma mansoni infections}},
author = {Miriam Bischofsberger and Tim A. Dannenhaus and Sanja U. Schönberger and Emil C. Reisinger and Micha Löbermann and Martina Sombetzki},
journal = {PLOS Neglected Tropical Diseases},
year = {2026},
month = oct,
doi = {10.1371/journal.pntd.0014814},
url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014814},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - From first contact to challenge: Lung immune modulation by single-sex Schistosoma mansoni infections
AU - Miriam Bischofsberger
AU - Tim A. Dannenhaus
AU - Sanja U. Schönberger
AU - Emil C. Reisinger
AU - Micha Löbermann
AU - Martina Sombetzki
PY - 2026
DA - 2026/10/27
JO - PLOS Neglected Tropical Diseases
DO - 10.1371/journal.pntd.0014814
UR - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014814
AB - Background: Schistosomiasis is a chronic parasitic disease caused by blood flukes of the genus Schistosoma and remains a major public health concern in endemic regions. Following skin penetration, schistosomula migrate through multiple host tissues before maturing into adult worm within the mesenteric vasculature. Immunological priming critically influences host responses during secondary infections, yet the importance of prior single-sex Schistosoma mansoni infection on pulmonary recall immunity remains largely unknown. Since the lungs serve as an important immunological checkpoint during schistosomula migration, we herein investigated how single-sex and bisexual priming influence the pulmonary immune landscape upon reinfection. Methodology: Using a murine reinfection model, mice were infected with male, female or mixed-sex S. mansoni cercariae and subsequently challenged with a bisexual infection. Pulmonary immune responses were analyzed by expression of key-regulatory genes, high-dimensional flow cytometry, tSNE/FlowSOM clustering and immune cell phenotyping. Conclusions: Single-sex priming resulted in distinct immune responses compared to bisexual infection. Male priming was associated with reduced pulmonary worm burden and a preferential enrichment of circulating CD4+ central and effector memory T cells, whereas female priming promoted the accumulation of CD4+ resident memory T cells together with broader alterations in pulmonary myeloid cell populations. Our findings demonstrate that the sex of primary Schistosoma mansoni infection differently programs pulmonary immune recall responses, particularly through distinct organization of the CD4+ memory T cell compartment. The association between male priming, enrichment of circulating memory T cell subsets and reduced pulmonary worm burden identifies pulmonary memory T cell organization as a potential correlate of protection during reinfection. Author summary: The present study demonstrated that single-sex Schistosoma mansoni priming profoundly shapes the pulmonary immune response upon subsequent bisexual challenge infection. Building upon previous observations that single-sex infections differently affect hepatic pathology, we investigated whether these priming effects are already detectable during the critical pulmonary migration phase of reinfection.
SN - 1935-2735
SN - 1935-2727
ER -