Certad Gabriela
U1019-UMR 9017-CIIL-Centre d'Infection et d'Immunité de Lille, Institut Pasteur de Lille, Université de Lille, CNRS, Inserm, CHU Lille, F-59000 Lille, France.
Délégation à la Recherche Clinique et à l'Innovation, Groupement des Hôpitaux de l'Institut Catholique de Lille, F-59462 Lomme, France.
Food Waterborne Parasitol. 2022 Apr 14;27:e00153. doi: 10.1016/j.fawpar.2022.e00153. eCollection 2022 Jun.
The pathophysiological mechanisms of infection are multifactorial and not completely understood. Some advances achieved recently revealed that the infection by induces cytoskeleton remodeling and actin reorganization through the implication of several intracellular signals involving, for example, PI3K, Src, Cdc42 and GTPases. It has also been reported that the infection by leads to the activation of NF-κβ, known to induce anti-apoptotic mechanisms and to transmit oncogenic signals to epithelial cells. Despite the growing evidence about the hijacking of cellular pathways, potentially being involved in cancer onset, this information has rarely been linked to the tumorigenic potential of the parasite. However, several evidences support an association between infection and the development of digestive neoplasia. To explore the dynamics of infection, an animal model of cryptosporidiosis using corticoid dexamethasone-treated adult SCID (severe combined immunodeficiency) mice, orally infected with or oocysts was implemented. -infected animals developed digestive adenocarcinoma. When mechanisms involved in this neoplastic process were explored, the pivotal role of the Wnt pathway together with the alteration of the cytoskeleton was confirmed. Recently, a microarray assay allowed the detection of cancer-promoting genes and pathways highly up regulated in the group of infected animals when compared to non-infected controls. Moreover, different human cases/control studies reported significant higher prevalence of infection among patients with recently diagnosed colon cancer before any treatment when compared to the control group (patients without colon neoplasia but with persistent digestive symptoms). These results suggest that is a potential oncogenic agent involved in cancer development beyond the usual suspects. If is able to hijack signal transduction, then is very likely that this contributes to transformation of its host cell. More research in the field is required in order to identify mechanisms and molecular factors involved in this process and to develop effective treatment interventions.
感染的病理生理机制是多因素的，尚未完全明确。最近取得的一些进展表明，[病原体名称]感染通过涉及多种细胞内信号（如PI3K、Src、Cdc42和GTPases）诱导细胞骨架重塑和肌动蛋白重排。也有报道称，[病原体名称]感染会导致NF-κβ激活，已知NF-κβ可诱导抗凋亡机制并向上皮细胞传递致癌信号。尽管越来越多的证据表明细胞途径被劫持可能与癌症发生有关，但这些信息很少与该寄生虫的致瘤潜力联系起来。然而，有多项证据支持[病原体名称]感染与消化系肿瘤发生之间存在关联。为探究[病原体名称]感染的动态变化，构建了一种隐孢子虫病动物模型，使用经皮质类固醇地塞米松处理的成年SCID（严重联合免疫缺陷）小鼠，经口感染[病原体名称]或[病原体名称]卵囊。感染[病原体名称]的动物发生了消化腺癌。当探究这一肿瘤形成过程中涉及的机制时，证实了Wnt途径的关键作用以及细胞骨架的改变。最近，一项微阵列分析检测到，与未感染的对照组相比，感染[病原体名称]的动物组中促进癌症的基因和途径高度上调。此外，不同的人类病例/对照研究报告称，与对照组（无结肠肿瘤但有持续消化症状的患者）相比，近期诊断为结肠癌且未接受任何治疗的患者中[病原体名称]感染的患病率显著更高。这些结果表明，[病原体名称]是一种潜在的致癌因子，在癌症发展中起着超乎寻常的作用。如果[病原体名称]能够劫持信号转导，那么很可能这有助于其宿主细胞的转化。该领域需要更多研究，以确定这一过程中涉及的机制和分子因素，并开发有效的治疗干预措施。
