Department of Molecular Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
Infect Immun. 2010 Aug;78(8):3369-77. doi: 10.1128/IAI.00292-10. Epub 2010 Jun 1.
Salmonella enterica serotype Typhimurium is a natural pathogen of mice, which acquire the bacteria orally and develop systemic acute infections that can become subacute to chronic infections. S. Typhimurium can reside within hemophagocytic macrophages (HMs) in SV129S6 mice, an Slc11a1/Nramp1(+/+) inbred strain. HMs are activated macrophages which have ingested viable hematopoietic cells and are a key characteristic of infectious and inflammatory diseases. Here we show that modest S. Typhimurium replication in HMs begins at 18 h postinfection, while activated macrophages kill the bacteria. For bacterial replication to occur, the phagocytosed viable cells must be grown to a low cell density and the multiplicity of infection must be low. HMs are able to kill phagocytosed Escherichia coli, produce reactive nitrogen species, and retain S. Typhimurium within membrane-bound vesicles. S. Typhimurium does not rescue E. coli upon coinfection of HMs. This indicates that S. Typhimurium does not cause HMs to become permissive for other microbes; rather, S. Typhimurium is especially equipped to survive within HMs. Two type three secretion systems (T3SS) encoded by S. Typhimurium are required for replication within HMs. While the T3SS within Salmonella pathogenicity island 2 (SPI-2) has been previously shown to be important for bacterial survival in cells, a role for SPI-1 in replication in macrophages has not been reported. The requirement for SPI-1 in HMs may help explain the role of SPI-1 during long-term colonization of mice.
鼠伤寒沙门氏菌血清型 Typhimurium 是一种天然的鼠类病原体，可经口服感染并引发全身性急性感染，随后转为亚急性至慢性感染。沙门氏菌可存在于 SV129S6 小鼠（Slc11a1/Nramp1[+/+]近交系）的噬血细胞巨噬细胞（HM）中。HM 是吞噬了活造血细胞的活化巨噬细胞，是感染和炎症性疾病的一个关键特征。本研究表明，HM 中适度的鼠伤寒沙门氏菌复制始于感染后 18 小时，此时活化的巨噬细胞会杀死细菌。为了发生细菌复制，被吞噬的活细胞必须生长到低细胞密度，并且感染复数必须较低。HM 能够杀死吞噬的大肠杆菌，产生活性氮物种，并将鼠伤寒沙门氏菌保留在膜结合囊泡内。当 HM 被共同感染时，鼠伤寒沙门氏菌不会拯救大肠杆菌。这表明鼠伤寒沙门氏菌不会使 HM 对其他微生物变得易感；相反，鼠伤寒沙门氏菌特别适合在 HM 内生存。鼠伤寒沙门氏菌编码的两种 III 型分泌系统（T3SS）对于在 HM 内的复制是必需的。尽管先前已经表明，沙门氏菌致病岛 2（SPI-2）内的 T3SS 对于细菌在细胞中的存活很重要，但 SPI-1 在巨噬细胞中复制的作用尚未报道。SPI-1 在 HM 中的需求可能有助于解释 SPI-1 在长期定植于小鼠期间的作用。
