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Persistent Cutaneous Leishmania major Infection Promotes Infection‐Adapted Myelopoiesis


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Ferreira, Fabio Luiz Bandeira; Séguin, Olivier; Descoteaux, Albert ORCID logoORCID: https://orcid.org/0000-0002-0633-5309 et Heinonen, Krista M. ORCID logoORCID: https://orcid.org/0000-0002-2410-4432 (2022). Persistent Cutaneous Leishmania major Infection Promotes Infection‐Adapted Myelopoiesis Microorganisms , vol. 10 , nº 3:535. pp. 1-17. DOI: 10.3390/microorganisms10030535.

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Hematopoietic stem/progenitor cells (HSPC) are responsible for the generation of most immune cells throughout the lifespan of the organism. Inflammation can activate bone marrow HSPCs, leading to enhanced myelopoiesis to replace cells, such as neutrophils, which are attracted to inflamed tissues. We have previously shown that HSPC activation promotes parasite persistence and expansion in experimental visceral leishmaniasis through the increased production of permissive monocytes. However, it is not clear if the presence of the parasite in the bone marrow was required for infection‐adapted myelopoiesis. We therefore hypothesized that persistent forms of Leishmania major (cutaneous leishmaniasis) could also activate HSPCs and myeloid precursors in the C57Bl/6 mouse model of intradermal infection in the ear. The accrued influx of myeloid cells to the lesion site corresponded to an increase in myeloid‐biased HSPCs in the bone marrow and spleen in mice infected with a persistent strain of L. major, together with an increase in monocytes and mon-ocyte‐derived myeloid cells in the spleen. Analysis of the bone marrow cytokine and chemokine environment revealed an attenuated type I and type II interferon response in the mice infected with the persistent strain compared to the self‐healing strain, while both strains induced a rapid upreg-ulation of myelopoietic cytokines, such as IL‐1β and GM‐CSF. These results demonstrate that an active infection in the bone marrow is not necessary for the induction of infection‐adapted myelo-poiesis, and underline the importance of considering alterations to the bone marrow output when analyzing in vivo host-pathogen interactions. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Type de document: Article
Mots-clés libres: Leishmania major; cutaneous leishmaniasis; hematopoietic stem/progenitor cell; inflammation; myelopoiesis
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 10 juill. 2022 14:08
Dernière modification: 10 juill. 2022 14:08
URI: https://espace.inrs.ca/id/eprint/12758

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