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Nitric oxide controls proliferation of Leishmania major by inhibiting the recruitment of permissive host cells.
Formaglio, Pauline Alabdullah, Mohamad Siokis, Anastasios Handschuh, Juliane Sauerland, Ina Fu, Yan Krone, Anna Gintschel, Patricia Stettin, Juliane Heyde, Sandrina
Formaglio, Pauline
Alabdullah, Mohamad
Siokis, Anastasios
Handschuh, Juliane
Sauerland, Ina
Fu, Yan
Krone, Anna
Gintschel, Patricia
Stettin, Juliane
Heyde, Sandrina
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2021-10-15
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Abstract
Nitric oxide (NO) is an important antimicrobial effector but also prevents unnecessary tissue damage by shutting down the recruitment of monocyte-derived phagocytes. Intracellular pathogens such as Leishmania major can hijack these cells as a niche for replication. Thus, NO might exert containment by restricting the availability of the cellular niche required for efficient pathogen proliferation. However, such indirect modes of action remain to be established. By combining mathematical modeling with intravital 2-photon biosensors of pathogen viability and proliferation, we show that low L. major proliferation results not from direct NO impact on the pathogen but from reduced availability of proliferation-permissive host cells. Although inhibiting NO production increases recruitment of these cells, and thus pathogen proliferation, blocking cell recruitment uncouples the NO effect from pathogen proliferation. Therefore, NO fulfills two distinct functions for L. major containment: permitting direct killing and restricting the supply of proliferation-permissive host cells.
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mmunity. 2021 Oct 15:S1074-7613(21)00406-4. doi: 10.1016/j.immuni.2021.09.021. Epub ahead of print.
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en
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1097-4180
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Attribution 4.0 International