Lymphotoxin beta receptor-/- mice display altered B- and T-cell subpopulations in the bone marrow and peritoneal cavity after Toxoplasma gondii infection

Helle M, Sorg UR, Ptok J, Thomas RE, Pracht K, Petzsch P, de Bruin A, Jäck HM, Köhrer K, Degrandi D, Pfeffer K (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Infection and Immunity American Society for Microbiology

Book Volume: 93

Pages Range: e0040825-

Journal Issue: 10

DOI: 10.1128/iai.00408-25

Abstract

Lymphotoxin β receptor (LTβR/TNFRSF3) signaling plays a crucial role in immune defense. Notably, LTβR-deficient (LTβR-/-) mice exhibit severe defects in innate and adaptive immunity against various pathogens and succumb to Toxoplasma gondii infection. Here, we investigated the bone marrow (BM) and peritoneal cavity (PerC) compartments of LTβR-/- mice during T. gondii infection, demonstrating perturbed B-cell and T-cell subpopulations in the absence of LTβR signaling. T. gondii infection disrupted BM lymphopoiesis, depleting early and mature B cells in WT mice, whereas mature B cells remained present in LTβR-/- BM. LTβR-/- BM also exhibited reduced MHCII+ monocytes and a plasma cell compartment skewed toward IgM+ rather than IgA+ cells. In addition, BM Tcell subsets were altered, exhibiting decreased double-negative (CD4-/CD8-) and increased CD4+ and CD8+ T-cell frequencies. Analysis of the BM transcriptome revealed diminished interferon responses but an upregulated TNFα-NF-κB signaling signature in uninfected and infected LTβR-/- mice, potentially compensating for the absence of LTβR signaling. LTβR-/- mice displayed an altered B-1a to B-1b ratio and a predominant presence of neutrophils in the PerC. In summary, we identified novel immunological alterations in the BM and PerC compartments of LTβR-/- mice, which suggest new roles for LTβR signaling in B- and T-cell homeostasis, migration, and pathogen defense.

Authors with CRIS profile

Katharina Pracht Department of Molecular Immunology Hans-Martin Jäck Department of Molecular Immunology

Involved external institutions

Heinrich-Heine-Universität Düsseldorf DE Germany (DE) Universiteit Utrecht (UU) / Utrecht University NL Netherlands (NL)

How to cite

APA:

Helle, M., Sorg, U.R., Ptok, J., Thomas, R.E., Pracht, K., Petzsch, P.,... Pfeffer, K. (2025). Lymphotoxin beta receptor-/- mice display altered B- and T-cell subpopulations in the bone marrow and peritoneal cavity after Toxoplasma gondii infection. Infection and Immunity, 93(10), e0040825-. https://doi.org/10.1128/iai.00408-25

MLA:

Helle, Marcel, et al. "Lymphotoxin beta receptor-/- mice display altered B- and T-cell subpopulations in the bone marrow and peritoneal cavity after Toxoplasma gondii infection." Infection and Immunity 93.10 (2025): e0040825-.

BibTeX: Download