Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis

PLoS Pathogens

Krista M. Heinonen¹  Belma Melda Abidin²  Simona Stäger²  Akil Hammami² 

[1] Centre for Host-Parasite interactions, Laval, Québec, Canada;INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada

关键词: Parasitic diseases;    Monocytes;    Bone marrow cells;    Flow cytometry;    Macrophages;    Spleen;    Leishmania donovani;    Bone marrow;   

DOI  :  10.1371/journal.ppat.1006422

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Cells of the immune system are derived from hematopoietic stem cells (HSCs) residing in the bone marrow. HSCs become activated in response to stress, such as acute infections, which adapt the bone marrow output to the needs of the immune response. However, the impact of infection-adapted HSC activation and differentiation on the persistence of chronic infections is poorly understood. We have examined here the bone marrow outcome of chronic visceral leishmaniasis and show that the parasite Leishmania donovani induces HSC expansion and skews their differentiation towards non-classical myeloid progenitors with a regulatory phenotype. Our results further suggest that emergency hematopoiesis contributes to the pathogenesis of visceral leishmaniasis, as decreased HSC expansion results in a lower parasite burden. Conversely, monocytes derived in the presence of soluble factors from the infected bone marrow environment are more permissive to infection by Leishmania. Our results demonstrate that L. donovani is able to subvert host bone marrow emergency responses to facilitate parasite persistence, and put forward hematopoiesis as a novel therapeutic target in chronic infections.

【 授权许可】

CC BY