Nash Evelyn E, Peters Brian M, Palmer Glen E, Fidel Paul L, Noverr Mairi C
Department of Microbiology, Immunology, and Parasitology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Department of Oral and Craniofacial Biology, Dental School, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Infect Immun. 2014 Aug;82(8):3426-35. doi: 10.1128/IAI.01746-14. Epub 2014 Jun 2.
Intra-abdominal polymicrobial infections cause significant morbidity and mortality. An established experimental mouse model of Staphylococcus aureus-Candida albicans intra-abdominal infection results in ∼60% mortality within 48 h postinoculation, concomitant with amplified local inflammatory responses, while monomicrobial infections are avirulent. The purpose of this study was to characterize early local and systemic innate responses during coinfection and determine the role of C. albicans morphogenesis in lethality, a trait involved in virulence and physical interaction with S. aureus. Local and systemic proinflammatory cytokines were significantly elevated during coinfection at early time points (4 to 12 h) compared to those in monoinfection. In contrast, microbial burdens in the organs and peritoneal lavage fluid were similar between mono- and coinfected animals through 24 h, as was peritoneal neutrophil infiltration. After optimizing the model for 100% mortality within 48 h, using 3.5 × 10(7) C. albicans (5× increase), coinfection with C. albicans yeast-locked or hypha-locked mutants showed similar mortality, dissemination, and local and systemic inflammation to the isogenic control. However, coinfection with the yeast-locked C. albicans mutant given intravenously (i.v.) and S. aureus given intraperitoneally (i.p.) failed to induce mortality. These results suggest a unique intra-abdominal interaction between the host and C. albicans-S. aureus that results in strong inflammatory responses, dissemination, and lethal sepsis, independent of C. albicans morphogenesis.
腹腔内多种微生物感染会导致显著的发病率和死亡率。一种已建立的金黄色葡萄球菌-白色念珠菌腹腔内感染实验小鼠模型在接种后48小时内导致约60%的死亡率，同时伴有局部炎症反应增强，而单一微生物感染则无致病性。本研究的目的是描述共感染期间早期局部和全身的固有免疫反应，并确定白色念珠菌形态发生在致死性中的作用，致死性是一种与毒力以及与金黄色葡萄球菌的物理相互作用有关的特性。与单一感染相比，共感染在早期时间点（4至12小时）局部和全身促炎细胞因子显著升高。相反，在24小时内，单一感染和共感染动物的器官及腹腔灌洗液中的微生物负荷相似，腹腔中性粒细胞浸润情况也相似。在用3.5×10⁷白色念珠菌（增加5倍）将模型优化至48小时内100%死亡率后，与白色念珠菌酵母锁定或菌丝锁定突变体共感染显示出与同基因对照相似的死亡率、播散以及局部和全身炎症。然而，静脉注射（i.v.）白色念珠菌酵母锁定突变体与腹腔注射（i.p.）金黄色葡萄球菌共感染未能诱导死亡。这些结果表明宿主与白色念珠菌-金黄色葡萄球菌之间存在独特的腹腔内相互作用，导致强烈的炎症反应、播散和致死性败血症，且与白色念珠菌形态发生无关。
