Théodorou I, Combadière C, Faure S, Debré P
Laboratoire d'Immunologie Cellulaire et Tissulaire-INSERM U543 Pitié-Salpêtrière, 83, bd de l'Hôpital, 75013 Paris, France.
J Soc Biol. 2002;196(1):7-11.
The genetic control of HIV infection by the host involves a certain number of genes, among which those which code for chemokines/chemokines receptors, cytokines, MHC. Genes such as CCR5, CCR2, SDF1, and more recently CX3CR1 received great attention from several laboratories including ours, since they play a role as HIV coreceptor and, as such, on the infectivity of the host. In addition, it was shown that the polymorphism of these genes influences the evolution of infection, whether they have a protective or deleterious effect. Results obtained by our laboratory on the genetic polymorphism and its implication in HIV infection will be reported herein. Furthermore, to better understand their role, we looked for the capacities that the chemokines may have to play an immunomodulatory function, independently of their chemoattractive effect. In two examples, we showed that chemokines influence notably the cellular immune functions, such as CD8 cytotoxicity (Rantes/CCR3) and gamma interferon production (fractalkine/CX3CR1). Globally, the results indicate that chemokines/chemokines receptors polymorphism represent important epidemiological factors, but also contributes to evaluate the prognosis of HIV infection, through a better understanding of the disease physiopathology.
宿主对HIV感染的基因控制涉及一定数量的基因,其中编码趋化因子/趋化因子受体、细胞因子、MHC的基因。诸如CCR5、CCR2、SDF1以及最近的CX3CR1等基因受到了包括我们实验室在内的多个实验室的极大关注,因为它们作为HIV共受体发挥作用,进而影响宿主的感染性。此外,研究表明这些基因的多态性会影响感染的进程,无论它们具有保护作用还是有害作用。本文将报道我们实验室关于基因多态性及其在HIV感染中的意义所获得的结果。此外,为了更好地理解它们的作用,我们探究了趋化因子可能具有的独立于其趋化作用的免疫调节功能。在两个实例中,我们表明趋化因子显著影响细胞免疫功能,如CD8细胞毒性(RANTES/CCR3)和γ干扰素产生(fractalkine/CX3CR1)。总体而言,结果表明趋化因子/趋化因子受体多态性不仅是重要的流行病学因素,还通过更好地理解疾病病理生理学,有助于评估HIV感染的预后。