HIF-1α is a key regulator in potentiating suppressor activity and limiting the microbicidal capacity of MDSC-like cells during visceral leishmaniasis

PLoS Pathogens

Krista M. Heinonen¹  Aymeric Fabié¹  Belma Melda Abidin¹  Tania Charpentier¹  Annie-Pier Duguay¹  Simona Stäger¹  Akil Hammami¹ 

[1] INRS-Institut Armand-Frappier and Center for Host-Parasite interactions, 531 Boulevard des Prairies, Laval (QC), Canada

关键词: Monocytes;    Bone marrow cells;    Leishmania donovani;    Parasitic diseases;    Spleen;    Macrophages;    Neutrophils;    Amastigotes;   

DOI  :  10.1371/journal.ppat.1006616

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Leishmania donovani is known to induce myelopoiesis and to dramatically increase extramedullary myelopoiesis. This results in splenomegaly, which is then accompanied by disruption of the splenic microarchitecture, a chronic inflammatory environment, and immunosuppression. Chronically inflamed tissues are typically hypoxic. The role of hypoxia on myeloid cell functions during visceral leishmaniasis has not yet been studied. Here we show that L. donovani promotes the output from the bone marrow of monocytes with a regulatory phenotype that function as safe targets for the parasite. We also demonstrate that splenic myeloid cells acquire MDSC-like function in a HIF-1α-dependent manner. HIF-1α is also involved in driving the polarization towards M2-like macrophages and rendering intermediate stage monocytes more susceptible to L. donovani infection. Our results suggest that HIF-1α is a major player in the establishment of chronic Leishmania infection and is crucial for enhancing immunosuppressive functions and lowering leishmanicidal capacity of myeloid cells.

【 授权许可】

CC BY