High Kevin P, Prasad Rajeev, Marion Chad R, Schurig Gerhardt G, Boyle Stephen M, Sriranganathan Nammalwar
Section of Infectious Diseases, Department of Internal Medicine, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA.
Biogerontology. 2007 Oct;8(5):583-93. doi: 10.1007/s10522-007-9106-6. Epub 2007 Jul 26.
Aging results in a general waning of immunity and enhanced susceptibility to many intracellular pathogens. However, in some instances, aging is accompanied by alternative immune responses that can be equal to, or even more effective, than those of young adults. Brucella spp. are intracellular bacteria and important human and animal pathogens, but there are no data regarding the effect of age on host defense in brucellosis. Young or old adult mice (DBA/2 or BALB/c) were infected with either an attenuated B. abortus strain that over-expressed the Brucella superoxide dismutase (strain RB51-SOD) or a fully virulent strain (strain 2308). Survival, organism burden in the spleen, and immune responses were assessed. All young adult and aged mice survived infection with RB51-SOD (up to 6 x 10(8) cfu) or strain 2308 (up to 8 x 10(8) cfu). Old mice had a lower organism burden in the spleen than young adult mice five or more weeks after infection. Antibody and cytokine responses were Th1-focused in young adult mice, but Th-mixed in older mice, including evidence of the newly defined Th17 subtype immune response. Immunization with the RB51-SOD strain provided protection vs. strain 2308 challenge in young and aged BALB/c, but only young adult DBA/2 mice. Thus, clinical outcomes of Brucella infection in aged mice are equal or superior to those of young adult mice; immune responses in older mice are less-Th1 specific suggesting alternate pathways may contribute to host defense vs. Brucella in aged mice.
衰老会导致免疫力普遍下降,以及对许多细胞内病原体的易感性增强。然而,在某些情况下,衰老会伴随着替代性免疫反应,这些反应可能与年轻成年人的免疫反应相当,甚至更有效。布鲁氏菌属是细胞内细菌,也是重要的人类和动物病原体,但目前尚无关于年龄对布鲁氏菌病宿主防御影响的数据。用过量表达布鲁氏菌超氧化物歧化酶的减毒流产布鲁氏菌菌株(RB51-SOD菌株)或完全有毒力的菌株(2308菌株)感染年轻或年老的成年小鼠(DBA/2或BALB/c)。评估存活率、脾脏中的病原体负荷和免疫反应。所有年轻成年和老年小鼠在感染RB51-SOD(高达6×10⁸ cfu)或2308菌株(高达8×10⁸ cfu)后均存活。感染后五周或更长时间,老年小鼠脾脏中的病原体负荷低于年轻成年小鼠。年轻成年小鼠的抗体和细胞因子反应以Th1为主,但老年小鼠的反应是Th混合性的,包括新定义的Th17亚型免疫反应的证据。用RB51-SOD菌株免疫可在年轻和老年BALB/c小鼠中提供针对2308菌株攻击的保护,但仅在年轻成年DBA/2小鼠中有效。因此,老年小鼠布鲁氏菌感染的临床结果与年轻成年小鼠相当或更好;老年小鼠的免疫反应Th1特异性较低,这表明替代途径可能有助于老年小鼠抵御布鲁氏菌。