Single-Sex Schistosome Infections Rewire Lung Memory T Cells on Rechallenge

In a mouse study published in PLOS Neglected Tropical Diseases, researchers report that the sex composition of a primary Schistosoma mansoni infection shapes how the lungs respond to reinfection. Mice primed with male, female, or mixed-sex cercariae were later challenged with a bisexual infection, and their pulmonary immune landscapes were compared using gene expression analysis, high-dimensional flow cytometry, tSNE/FlowSOM clustering, and immune cell phenotyping.

Male priming was associated with a reduced pulmonary worm burden upon challenge and with a preferential enrichment of circulating CD4+ central and effector memory T cells in the lung. Female priming, by contrast, promoted the accumulation of CD4+ resident memory T cells and was accompanied by broader alterations in the pulmonary myeloid cell population.

Schistosomiasis remains a major public health concern in endemic regions. After penetrating the skin, schistosomula migrate through several host tissues, including the lungs, before maturing into adult worms in the mesenteric vasculature. Because this pulmonary passage acts as an important immunological checkpoint, the authors investigated whether prior exposure to only one sex of parasite could reprogram recall immunity at this site—a question they note had remained largely unexplored.

The study’s central observation is an association: male priming, enrichment of circulating memory T cell subsets in the lung, and lower pulmonary worm burden occurred together, leading the authors to propose that the organization of the pulmonary CD4+ memory T cell compartment may serve as a potential correlate of protection during reinfection. Female priming instead shifted the memory landscape toward tissue-resident CD4+ T cells alongside wider changes in myeloid populations, indicating that the two single-sex conditions program recall immunity in fundamentally different ways.

The findings come from a laboratory reinfection model, so the correlations reflect murine responses rather than demonstrated protective mechanisms in humans. Nonetheless, the authors conclude that the sex of the primary S. mansoni infection differentially programs pulmonary immune recall responses, particularly through distinct organization of the CD4+ memory T cell compartment, and that pulmonary memory T cell organization deserves further attention as a possible marker of protection against reinfection.

Subject of Research: How single-sex versus bisexual Schistosoma mansoni priming alters pulmonary immune recall responses in mice

Article Title: From first contact to challenge: Lung immune modulation by single-sex Schistosoma mansoni infections

Article References: Bischofsberger, M., Dannenhaus, T. A., Schönberger, S. U., Reisinger, E. C., Löbermann, M., & Sombetzki, M. (2026). From first contact to challenge: Lung immune modulation by single-sex Schistosoma mansoni infections. PLOS Neglected Tropical Diseases, 20(10), e0014814. https://doi.org/10.1371/journal.pntd.0014814

Image Credits: AI Generated

DOI: 10.1371/journal.pntd.0014814

Keywords: schistosomiasis, Schistosoma mansoni, lung immunity, CD4 memory T cells, reinfection, mouse model, immunology, parasitology, flow cytometry, worm burden, first, contact