Both maternal IFNγ exposure and acute prenatal infection with Toxoplasma gondii activate fetal hematopoietic stem cells.

Autor: López DA; Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA., Otsuka KS; Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA., Apostol AC; Quantitative and Systems Biology Graduate Program, University of California, Merced, Merced, CA, USA., Posada J; Department of Molecular and Cell Biology, University of California, Merced, Merced, CA, USA., Sánchez-Arcila JC; Department of Molecular and Cell Biology, University of California, Merced, Merced, CA, USA., Jensen KD; Department of Molecular and Cell Biology, University of California, Merced, Merced, CA, USA.; Health Science Research Institute, University of California, Merced, Merced, CA, USA., Beaudin AE; Departments of Internal Medicine and Pathology, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2023 Jul 17; Vol. 42 (14), pp. e112693. Date of Electronic Publication: 2023 Jun 01.
DOI: 10.15252/embj.2022112693
Abstrakt: Infection directly influences adult hematopoietic stem cell (HSC) function and differentiation, but the fetal hematopoietic response to infection during pregnancy is not well-studied. Here, we investigated the fetal hematopoietic response to maternal infection with Toxoplasma gondii (T. gondii), an intracellular parasite that elicits Type II IFNγ-mediated maternal immunity. While it is known that maternal infection without direct pathogen transmission can affect fetal immune development, the effects of maternal IFNγ on developing HSCs and the signals that mediate these interactions have not been investigated. Our investigation reveals that the fetal HSCs respond to T. gondii infection with virulence-dependent changes in proliferation, self-renewal potential, and lineage output. Furthermore, maternal IFNγ crosses the fetal-maternal interface, where it is perceived by fetal HSCs. By comparing the effects of maternal IFNγ injection with maternal T. gondii infection, we reveal that the effects of IFNγ treatment mimic some aspects of the fetal HSC response to infection. Moreover, our findings illuminate that the fetal HSC response to prenatal infection is distinct from the adult HSC response to IFNγ-induced inflammation. Altogether, our data disentangle the role of infection-induced inflammatory cytokines in driving the expansion of downstream hematopoietic progenitors.
(© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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