Talaat Kawsar R, Bonawitz Rachael E, Domenech Pilar, Nutman Thomas B
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Infect Dis. 2006 Jan 15;193(2):196-204. doi: 10.1086/498912. Epub 2005 Dec 13.
Mycobacterium tuberculosis and helminth coinfection is highly prevalent, and the presence of helminths may modulate the Th1 response necessary for M. tuberculosis control.
Elutriated human monocytes, differentiated into dendritic cells (DCs) and macrophages, were exposed in vitro to live microfilariae (mf). The influence that mf had on M. tuberculosis infectivity, expression of cell surface molecules, and production of cytokines was determined.
Compared with mf-unexposed, M. tuberculosis-infected cells, mf-exposed, M. tuberculosis-infected DCs had decreased expression of CD14, CD54, and human leukocyte antigen-DR, and mf-exposed, M. tuberculosis-infected macrophages had decreased expression of CD40. DCs that were mf exposed and M. tuberculosis infected produced more interleukin (IL)-1 beta than did mf-unexposed, M. tuberculosis-infected DCs. Also, mf-exposed, M. tuberculosis-infected DCs and macrophages expressed less IL-10 and interferon (IFN)- alpha than did mf-unexposed, M. tuberculosis-infected cells. When they were cultured with autologous CD4+ T cells, mf-exposed, M. tuberculosis-infected DCs were less capable of stimulating the production of IFN- gamma than were other DCs. Exposure of DCs to mf decreased the surface expression of DC-specific intercellular adhesion molecule-3 grabbing nonintegrin, a receptor required by M. tuberculosis for entry into DCs.
Exposure to mf reduces a key receptor on the DC surface, which perhaps renders these cells less susceptible to infection with M. tuberculosis. Exposure to mf changes the surface expression of adhesion and costimulatory molecules on DCs and macrophages and alters their expression of cytokines and chemokines in a way that renders them less capable of immunologic responses.
结核分枝杆菌与蠕虫共感染非常普遍,蠕虫的存在可能会调节控制结核分枝杆菌所需的Th1反应。
将淘洗后的人单核细胞分化为树突状细胞(DCs)和巨噬细胞,在体外使其暴露于活的微丝蚴(mf)。确定mf对结核分枝杆菌感染性、细胞表面分子表达及细胞因子产生的影响。
与未暴露于mf的结核分枝杆菌感染细胞相比,暴露于mf的结核分枝杆菌感染的DCs中,CD14、CD54和人类白细胞抗原-DR的表达降低,暴露于mf的结核分枝杆菌感染的巨噬细胞中,CD40的表达降低。暴露于mf且感染结核分枝杆菌的DCs产生的白细胞介素(IL)-1β比未暴露于mf的结核分枝杆菌感染的DCs更多。此外,暴露于mf的结核分枝杆菌感染的DCs和巨噬细胞表达的IL-10和干扰素(IFN)-α比未暴露于mf的结核分枝杆菌感染的细胞更少。当与自体CD4+T细胞共培养时,暴露于mf的结核分枝杆菌感染的DCs刺激IFN-γ产生的能力低于其他DCs。DCs暴露于mf会降低DC特异性细胞间黏附分子-3结合非整合素的表面表达,该分子是结核分枝杆菌进入DCs所需的受体。
暴露于mf会减少DC表面的关键受体,这可能使这些细胞不易感染结核分枝杆菌。暴露于mf会改变DCs和巨噬细胞上黏附分子和共刺激分子的表面表达,并以使其免疫反应能力降低的方式改变它们的细胞因子和趋化因子表达。