Silverblatt F J
J Exp Med. 1974 Dec 1;140(6):1696-711. doi: 10.1084/jem.140.6.1696.
The initial interaction between bacteria and the renal pelvic epithelium may determine whether intrarenal infection occurs. A model of retrograde pyelonephritis was employed to study these events by electron microscopy. Female rats received an intravesicular inoculation of a 0.5-ml suspension of Proteus mirabilis containing 10(8) organisms. At intervals after inoculation, the kidneys were fixed by intravascular perfusion and the tissues were prepared for electron microscopy. During the first 24 h, increasing numbers of bacteria were seen to be attached by pili to the renal pelvic epithelial cells. The organism appeared to cross the mucosal barrier by several mechanisms: (a) penetration into the cytoplasm of intact epithelial cells, (b) passage between epithelial cells that were separated by excessive hydrostatic pressure generated during bladder inoculation, (c) passage across necrotic regions of the pelvis, and (d) translocation to the cortex by calicotubular backflow. Whereas at inoculation bacteria possessed pili 40 A in diameter (type III pili) 24 h after reflux, the predominant type of pili measured 70 A in thickness (type IV pili). Repetitive subculture induced a similar transition in vitro. To assess the influence of pili type on virulence in this model, 80 rats were challenged with either type III or type IV pilated organisms and the frequency of rats with cortical abscesses were compared at 1 wk. A significantly greater number of rats inoculated with type IV pilated Proteus manifested macroscopic evidence of infection. These results suggest that pili play a role in the pathogenesis of ascending pyelonephritis.
细菌与肾盂上皮细胞之间的初始相互作用可能决定是否会发生肾内感染。采用逆行肾盂肾炎模型,通过电子显微镜研究这些事件。雌性大鼠膀胱内接种含有10⁸个菌的0.5毫升奇异变形杆菌悬液。接种后每隔一定时间,通过血管内灌注固定肾脏,并制备组织用于电子显微镜观察。在最初的24小时内,可见越来越多的细菌通过菌毛附着在肾盂上皮细胞上。细菌似乎通过几种机制穿过黏膜屏障:(a)侵入完整上皮细胞的细胞质;(b)在膀胱接种期间因过高静水压而分离的上皮细胞之间通过;(c)穿过肾盂的坏死区域;(d)通过肾小盏小管逆流转移至皮质。接种时细菌具有直径40 Å的菌毛(III型菌毛),反流24小时后,主要的菌毛类型厚度为70 Å(IV型菌毛)。重复传代培养在体外诱导了类似的转变。为了评估该模型中菌毛类型对毒力的影响,用III型或IV型菌毛菌攻击80只大鼠,并在1周时比较出现皮质脓肿的大鼠频率。接种IV型菌毛奇异变形杆菌的大鼠中,出现感染宏观证据的数量明显更多。这些结果表明菌毛在上行性肾盂肾炎的发病机制中起作用。