Mucosal damage and neutropenia are required for Candida albicans dissemination.
Mucosal damage and neutropenia are required for Candida albicans dissemination.
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白色念珠菌传播需要粘膜损伤和中性粒细胞减少。
DOI：
10.1371/journal.ppat.0040035
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发表时间：
2008-02-08
期刊：
影响因子：
6.7
通讯作者：
Pier, Gerald B.
中科院分区：
文献类型：
--
作者：
Koh, Andrew Y.;Kohler, Julia R.;Coggshall, Kathleen T.;Van Rooijen, Nico;Pier, Gerald B.
癌症患者的白色念珠菌菌血症被认为是从最初的胃肠道(GI)定植发展起来的，随后在化疗后转移到血液中。目前尚不清楚先天免疫系统的哪些组成部分对于防止白色念珠菌从胃肠道传播是必需的，但我们假设中性粒细胞减少和胃肠道粘膜损伤都是导致广泛的侵袭性白色念珠菌疾病的关键。我们在白念珠菌胃肠道定植的小鼠模型中研究了这些参数，该模型在给药免疫抑制和粘膜损伤后导致全身扩散。在抗生素治疗耗尽肠道菌群并使白色念珠菌达到稳定的胃肠道定植水平后，环磷酰胺全身化疗可导致100%的死亡率，而选择性中性粒细胞耗竭、巨噬细胞耗竭、淋巴细胞减少或胃肠道粘膜破坏单独使用则不会导致死亡。选择性中性粒细胞去除合并胃肠道黏膜破坏导致播散性真菌感染，随后100%死亡。白念珠菌的胃肠道移位和传播也依赖于生物从酵母菌转化为菌丝体的能力。这种GI定植和真菌血症小鼠模型可用于研究预防侵袭性白念珠菌病所需的天然宿主免疫因素，以及识别真菌GI定植和传播所必需的毒力因子。该模型也可能被证明对评估控制白色念珠菌感染的治疗方法有价值。白色念珠菌是一种生活在人类胃肠道中的真菌，对人体无害。然而，在癌症患者和接受骨髓移植的患者中，给这些患者使用的抗癌药物也会导致抑制人类免疫系统的不良效果。这种疗法允许白色念珠菌扩散到血液和其他器官，并导致严重的疾病。我们发现，我们可以在带有白色念珠菌的小鼠的胃肠道定植，然后用抗癌药物抑制免疫系统，以确定天然免疫系统的哪些组件(中性粒细胞、淋巴细胞、巨噬细胞或胃肠道完整性)对于防止白色念珠菌从胃肠道飞来至关重要。我们发现，降低中性粒细胞计数和破坏胃肠道都是导致系统性白念珠菌感染所必需的。我们还发现，白色念珠菌从酵母(球形)形态转变为丝状形态的能力对于确定侵袭性疾病也是重要的。我们的研究为一旦宿主免疫系统的关键组成部分受到损害时，一种典型无害的微生物如何导致严重的侵袭性疾病的过程提供了新的见解。
Candida albicans fungemia in cancer patients is thought to develop from initial gastrointestinal (GI) colonization with subsequent translocation into the bloodstream after administration of chemotherapy. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but we have hypothesized that both neutropenia and GI mucosal damage are critical for allowing widespread invasive C. albicans disease. We investigated these parameters in a mouse model of C. albicans GI colonization that led to systemic spread after administration of immunosuppression and mucosal damage. After depleting resident GI intestinal flora with antibiotic treatment and achieving stable GI colonization levels of C. albicans, it was determined that systemic chemotherapy with cyclophosphamide led to 100% mortality, whereas selective neutrophil depletion, macrophage depletion, lymphopenia or GI mucosal disruption alone resulted in no mortality. Selective neutrophil depletion combined with GI mucosal disruption led to disseminated fungal infection and 100% mortality ensued. GI translocation and dissemination by C. albicans was also dependent on the organism's ability to transform from the yeast to the hyphal form. This mouse model of GI colonization and fungemia is useful for studying factors of innate host immunity needed to prevent invasive C. albicans disease as well as identifying virulence factors that are necessary for fungal GI colonization and dissemination. The model may also prove valuable for evaluating therapies to control C. albicans infections. Candida albicans is a fungus that lives harmlessly in the gastrointestinal (GI) tracts of humans. In cancer patients and patients undergoing bone marrow transplantation, however, the anti-cancer drugs that are administered to these patients also cause the undesired effect of suppressing the human immune system. The treatments allow C. albicans to spread into the blood and other organs and cause a severe disease. We found we could colonize the GI tracts of mice with C. albicans and then suppress the immune system with anti-cancer drugs to determine which components of the innate immune system (neutrophils, lymphocytes, macrophages, or GI tract integrity) are critical for preventing C. albicans from speading from the GI tract. We found that lowering the neutrophil counts and damaging the GI tract were both needed to cause systemic infection with C. albicans. We also found that the ability of C. albicans to switch from the yeast (spherical) form to the filamentous form is also important for establishing invasive disease. Our study provides new insights into the process of how a typically harmless microorganism inhabiting the GI tract can cause severe invasive disease once critical components of the host immune system are compromised.
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影响因子：
3.1
作者：
CENCI, E;ROMANI, L;BISTONI, F
通讯作者：
BISTONI, F
影响因子：
3.1
作者：
Bader, Teresa;Schroeppel, Klaus;Morschhaeuser, Joachim
通讯作者：
Morschhaeuser, Joachim
DOI：
10.1007/bf01967060
发表时间：
1992-02-01
影响因子：
4.5
作者：
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通讯作者：
VANTWOUT, J
影响因子：
4.9
作者：
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通讯作者：
Stevens, David A.
影响因子：
3.1
作者：
DEREPENTIGNY, L;PHANEUF, M;MATHIEU, LG
通讯作者：
MATHIEU, LG