Leishmania donovani metacyclic promastigotes impair phagosome properties in inflammatory monocytes

Matte, Christine; Arango Duque, Guillermo et Descoteaux, Albert ORCID: https://orcid.org/0000-0002-0633-5309 (2021). Leishmania donovani metacyclic promastigotes impair phagosome properties in inflammatory monocytes Infection and Immunity , vol. 89 , nº 7. pp. 1-14. DOI: 10.1128/iai.00009-21.

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Résumé

Leishmaniasis, a debilitating disease with clinical manifestations ranging from self-healing ulcers to life-threatening visceral pathologies, is caused by protozoan parasites of the Leishmania genus. These professional vacuolar pathogens are transmitted by infected sand flies to mammalian hosts as metacyclic promastigotes and are rapidly internalized by various phagocyte populations. Classical monocytes are among the first myeloid cells to migrate to infection sites. Recent evidence shows that recruitment of these cells contributes to parasite burden and to the establishment of chronic disease. However, the nature of Leishmania-inflammatory monocyte interactions during the early stages of host infection has not been well investigated. Here, we aimed to assess the impact of Leishmania donovani metacyclic promastigotes on antimicrobial responses within these cells. Our data showed that inflammatory monocytes are readily colonized by L. donovani metacyclic promastigotes, while infection with Escherichia coli is efficiently cleared. Upon internalization, metacyclic promastigotes inhibited superoxide production at the parasitophorous vacuole (PV) through a mechanism involving exclusion of NADPH oxidase subunits gp91 (phox) and p47 (phox) from the PV membrane. Moreover, we observed that unlike phagosomes enclosing zymosan particles, vacuoles containing parasites acidify poorly. Interestingly, whereas the parasite surface coat virulence glycolipid lipophosphoglycan (LPG) was responsible for the inhibition of PV acidification, impairment of the NADPH oxidase assembly was independent of LPG and GP63. Collectively, these observations indicate that permissiveness of inflammatory monocytes to L. donovani may thus be related to the ability of this parasite to impair the microbicidal properties of phagosomes.

Type de document:	Article
Informations complémentaires:	document e00009-21
Mots-clés libres:	Leishmania, NADPH Oxidase, Acidification, Inflammatory Monocytes, Phagosomes, Virulence Factors
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	22 juin 2022 19:41
Dernière modification:	22 juin 2022 19:41
URI:	https://espace.inrs.ca/id/eprint/12383

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