小鼠皮肤原发性隐球菌感染后的血行播散

Dissemination of primary cutaneous cryptococcosis in Balb/C mice

目的研究原发性小鼠新型隐球菌皮肤感染后产生的血行播散,检验皮肤作为隐球菌系统感染入侵的可能。方法新型隐球菌标准野生株B3501与ATCC32609分别皮内接种于环磷酰胺免疫抑制与非抑制的Balb/C小鼠,每组12只,待产生皮肤损伤后,分别于感染后1、2、4周处死,肝、胰、肾、脑、心、血液分别进行真菌培养,血清进行隐球菌荚膜抗原乳胶凝集试验。结果接种菌悬液后各组小鼠的接种部位形成皮肤损伤。环磷酰胺免疫抑制组和非抑制组皮肤损伤形成时间分别为3.42 d和4.25 d(P>0.05);皮肤损伤愈合时间分别为36.8 d和29.0 d(P<0.05)。在皮肤损伤形成后1、2、4周,各脏器和血液的真菌培养均为阴性。B3501、ATCC32609环磷酰胺处理组血清乳胶凝集试验阳性率分别为50%与17%,差异无统计学意义(P>0.05)。结论原发性皮肤隐球菌感染可能会导致免疫抑制的Balb/C小鼠血行播散。支持皮肤可能是隐球菌侵入机体的通道之一。

Objective To investigate the dissemination of cryptococcal infection after skin inoculation of cryptococcus neoformans and explore the possibility of skin as the route of entry into host by cryptococcus neoformans. Methods Immunocompromised Balb/C mouse model was made by administrating cyclophosphamide（CTX）. Balb/C mice, either immunocompromised or immunocompetent, were intradermaly inoculated with wild type cryptococcus neoformans variety neoformans B3501 or variety gattii ATCC32609. One, two, four weeks after the infection lesions appears, mycological culture was performed with liver, spleen, kidney, heart, brain and blood of the mice and latex agglutination test of cryptococcus antigen（LAT） was done with serum of the mice. Results Mean time of lesion appearance was 3.42 d in immunocompromised mice, 4.25 d in immunocompenent mice（P 〉 0.05）. Mean time for lesion healing in immunocompromised and immunocompenent mice was 36.8 d and 29.0 d respectively（P 〈 0.05）. Mycological tests were done with viscera tissues and blood samples at 1, 2 and 4 weeks after the lesion development. The culture results were all negative, while the positive rate of LAT was 50. 0% in B3501 group and 16.7% in ATCC32609 group（P 〉 0.05）. Conclusions Primary cutaneous cryptococcosis may lead to dissemination of the infection in immunocompromised mice and our data suggest that skin is a possible route for dissemination of cryptococcal infection.