Scott P, Sacks D, Sher A
J Immunol. 1983 Aug;131(2):966-71.
Cutaneous leishmaniasis can be either a spontaneously healing or chronic disease, depending upon the strain of parasite and the immunological status of the host. We have investigated parasite factors responsible for the variable pathogenesis observed in leishmanial infections by testing the sensitivity of several leishmanial strains to intracellular killing in lymphokine (LK) activated mouse macrophages. Significant microbicidal activity against Leishmania tropica, a strain which heals in C57BL/6 (B6) mice, was found. In contrast, a strain (Maria) which has previously been shown to induce chronic nonhealing cutaneous lesions in B6 mice was resistant to killing in activated macrophages. This resistance to killing was observed in macrophages activated by LK obtained from either Bacille Calmette-Guérin-, L. tropica, or the Maria strain infected mice. The inability of LK activated macrophages to kill the Maria strain was shown not to be due to parasite induced inhibition of killing mechanisms, since Maria strain infected, LK treated macrophages exhibited tumoricidial activity similar to uninfected macrophages. Furthermore, LK activated macrophages simultaneously infected with the Maria strain and another intracellular pathogen, Toxoplasma gondii, killed Toxoplasma, but not the Maria strain. Temperature was also found to significantly influence the multiplication and killing of Leishmania parasites. As would be expected from their cutaneous nature, L. tropica and Maria strain parasites multiplied better at 35 degrees C than at 37 degrees C. Also consistent with the failure of cutaneous strains to visceralize in immunocompetent mice was the observation that the killing of leishmanial parasites was enhanced at the higher temperature. Thus, the temperature dependent growth capacity and sensitivity to killing of a given leishmanial strain in macrophages may be important factors influencing the pathogenesis of cutaneous leishmaniasis.
皮肤利什曼病可以是一种自发愈合的疾病，也可以是慢性病，这取决于寄生虫的菌株和宿主的免疫状态。我们通过测试几种利什曼菌株对淋巴因子（LK）激活的小鼠巨噬细胞内杀伤作用的敏感性，研究了导致利什曼感染中观察到的不同发病机制的寄生虫因素。发现对热带利什曼原虫（一种在C57BL/6（B6）小鼠中可愈合的菌株）有显著的杀菌活性。相比之下，先前已证明在B6小鼠中可诱导慢性不愈合皮肤病变的一个菌株（Maria）对激活的巨噬细胞内的杀伤具有抗性。在用从卡介苗、热带利什曼原虫或感染Maria菌株的小鼠获得的LK激活的巨噬细胞中均观察到这种杀伤抗性。LK激活的巨噬细胞无法杀死Maria菌株并非由于寄生虫诱导的杀伤机制抑制，因为用LK处理的感染Maria菌株的巨噬细胞表现出与未感染巨噬细胞相似的杀肿瘤活性。此外，同时感染Maria菌株和另一种细胞内病原体弓形虫的LK激活巨噬细胞能杀死弓形虫，但不能杀死Maria菌株。还发现温度对利什曼寄生虫的增殖和杀伤有显著影响。正如从它们的皮肤特性所预期的那样，热带利什曼原虫和Maria菌株寄生虫在35℃比在37℃下增殖得更好。同样与皮肤菌株在免疫健全小鼠中不会内脏化的现象一致的是，在较高温度下利什曼寄生虫的杀伤作用增强。因此，给定利什曼菌株在巨噬细胞中温度依赖性的生长能力和对杀伤的敏感性可能是影响皮肤利什曼病发病机制的重要因素。
