Myeloid progenitors protect against invasive aspergillosis and Pseudomonas aeruginosa infection following hematopoietic stem cell transplantation
Myeloid progenitors protect against invasive aspergillosis and Pseudomonas aeruginosa infection following hematopoietic stem cell transplantation
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DOI：
10.1182/blood-2002-05-1552
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发表时间：
2002-12-15
期刊：
影响因子：
20.3
通讯作者：
Brown, JMY
中科院分区：
文献类型：
--
作者：
BitMansour, A;Burns, SM;Brown, JMY
肿瘤疾病的骨髓毒性治疗通常并发中性粒细胞减少症，这使患者容易受到潜在的致命感染。在这些小鼠造血干细胞移植（HSCT）的研究中，共移植谱系限制性祖细胞（称为共同髓样祖细胞（CMP）和粒细胞-单核细胞祖细胞（GMP））可防止2种与中性粒细胞减少症相关的病原体（烟曲霉菌和铜绿假单胞菌）的致死性攻击后死亡。CMP/GMP联合移植可使脾内髓系细胞绝对数量迅速增加，其中大部分来源于供体CMP/GMP。尽管持续性外周中性粒细胞减少，但生存率的提高与脾脏中祖细胞衍生的髓样细胞的可测量外观相关。通过培养证实组织病原体负荷的显著减少或消除与存活率相关。铜绿假单胞菌感染的定位和疾病的程度也通过体内生物发光成像进行了评估，使用铜绿假单胞菌菌株工程组成型表达细菌荧光素酶。影像学证实，含有造血干细胞和CMP/GMP的移植物的移植最早在感染后18小时就减少了细菌负荷。这些结果表明，增强重建的组织骨髓池提供保护，以防止致命的挑战与严重的真菌和细菌病原体。
Myelotoxic treatments for oncologic diseases are often complicated by neutropenia, which renders patients susceptible to potentially lethal infections. In these studies of murine hematopoietic stem cell transplantation (HSCT), cotransplantation of lineage-restricted progenitors known as common myeloid progenitors (CMP) and granulocyte-monocyte progenitors (GMP) protects against death following otherwise lethal challenge with either of 2 pathogens associated with neutropenia: Aspergillus fumigatus and Pseudomonas aeruginosa. Cotransplantation of CMP/GMP resulted in a significant and rapid increase in the absolute number of myeloid cells in the spleen, most of which were derived from the donor CMP/GMP. Despite persistent peripheral neutropenia, improved survival correlated with the measurable appearance of progenitor-derived myeloid cells in the spleen. A marked reduction or elimination of tissue pathogen load was confirmed by culture and correlated with survival. Localization of infection by P aeruginosa and extent of disease was also assessed by in vivo bioluminescent imaging using a strain of P aeruginosa engineered to constitutively express a bacterial luciferase. Imaging confirmed that transplantation with a graft containing hematopoietic stem cells and CMP/GMP reduced the bacterial load as early as 18 hours after infection. These results demonstrate that enhanced reconstitution of a tissue myeloid pool offers protection against lethal challenge with serious fungal and bacterial pathogens.