Gametocytes of the Malaria Parasite Plasmodium falciparum Interact With and Stimulate Bone Marrow Mesenchymal Cells to Secrete Angiogenetic Factors

Frontiers in Cellular and Infection Microbiology

Silvestrini, Francesco²  Falchi, Mario²  Valtieri, Mauro²  Alano, Pietro³  Messina, Valeria⁶  Rubio, Mercedes⁷  Mancini, Francesca⁸  Mayor, Alfredo^1,11 

[1] ã, Italy;AIDS National Center, Istituto Superiore di SanitàCentro de InvestigaçDipartimento di Biotecnologie Cellulari ed Ematologia, Umberto I - Policlinico di Roma, Italy;Dipartimento di Malattie Infettive, Istituto Superiore di SanitàDipartimento di Oncologia e Medicina Molecolare, Istituto Superiore di SanitàISGlobal, Barcelona Ctr. Int. Health Res, Hospital Clía, Mozambique;de da Manhiçnic - Universitat de Barcelona, Spain;o em Saú

关键词: Malaria;    Falciparum;    gametocytes;    Bone Marrow;    Host-Parasite Interactions;    Angiogenesis;   

DOI  :  10.3389/fcimb.2018.00050

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

The gametocytes of Plasmodium falciparum, responsible for the transmission of this malaria parasite from humans to mosquitoes, accumulate and mature preferentially in the human bone marrow. In the 10 day long sexual development of P. falciparum, the immature gametocytes reach and localize in the extravascular compartment of this organ, in contact with several bone marrow stroma cell types, prior to traversing the endothelial lining and re-entering in circulation at maturity. To investigate the host parasite interplay underlying this still obscure process, we developed an in vitro tridimensional co-culture system in a Matrigel scaffold with P. falciparum gametocytes and self-assembling spheroids of human bone marrow mesenchymal cells (hBM-MSCs). Here we show that this co-culture system sustains the full maturation of the gametocytes and that the immature, but not the mature, gametocytes adhere to hBM-MSCs via trypsin-sensitive parasite ligands exposed on the erythrocyte surface. Analysis of a time course of gametocytogenesis in the co-culture system revealed that gametocyte maturation is accompanied by the parasite induced stimulation of hBM-MSCs to secrete a panel of 13 cytokines and growth factors, 11 of which have been described to play a role in angiogenesis. Functional in vitro assays on human bone marrow endothelial cells showed that supernatants from the gametocyte mesenchymal cell co-culture system enhance ability of endothelial cells to form vascular tubes. These results altogether suggest that the interplay between immature gametocytes and hBM-MSCs may induce functional and structural alterations in the endothelial lining of the human bone marrow hosting the P. falciparum transmission stages.

【 授权许可】

CC BY