Protection against lethal sepsis following immunization with Candida species varies by isolate and inversely correlates with bone marrow tissue damage.
Protection against lethal sepsis following immunization with Candida species varies by isolate and inversely correlates with bone marrow tissue damage.
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DOI：
10.1128/iai.00252-23
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发表时间：
2023-10-17
影响因子：
3.1
通讯作者：
Fidel, Paul L., Jr.
中科院分区：
文献类型：
--
作者：
Lilly, Elizabeth A.;Bender, Breah E.;Noverr, Mairi C.;Fidel, Paul L., Jr.
通过一种新型训练有素的先天免疫 (TII) 可以预防致命的白色念珠菌 (Ca)/金黄色葡萄球菌 (Sa) 介导的败血症，该免疫涉及通过接种（免疫）低毒力念珠菌物种 [即都柏林念珠菌 (Cd)] 诱导的 Gr-1+ 骨髓源性抑制细胞 (MDSC)，浸润骨髓（BM）。相比之下，毒性更强的念珠菌物种（即白色念珠菌），即使在亚致死接种量下，也无法诱导类似水平的保护。本研究的目的是检验以下假设：Ca 菌株诱导的 TII 介导的保护水平与 BM 损伤呈负相关，作为毒力的反映。通过腹膜内接种几种缺乏毒力因子（菌丝形成和念珠菌溶素产生）的白色念珠菌亲本和突变株对小鼠进行免疫，然后在 14 天后进行腹膜内 Ca/Sa 攻击并监测败血症和死亡率。免疫后24小时和13天收集整个股骨，并通过铁死亡和组织学评估BM组织/细胞损伤。虽然使用大多数野生型白色念珠菌菌株的标准而非亚致死接种物进行免疫会导致相当大的死亡率，但不同菌株对致命 Ca/Sa IAI 攻击的保护通常低于都柏林念珠菌，在亲本和相应突变体之间没有观察到差异。最后，Ca 菌株提供的保护水平与 BM 组织损伤呈负相关 (R 2 = -0.773)。 TII 介导的针对念珠菌菌株免疫诱导的致死性 Ca/Sa 脓毒症的保护作用与 BM 组织/细胞损伤呈负相关，作为局部毒力的反映。
Protection against lethal Candida albicans (Ca)/Staphylococcus aureus (Sa) intra-abdominal infection (IAI)-mediated sepsis can be achieved by a novel form of trained innate immunity (TII) involving Gr-1+ myeloid-derived suppressor cells (MDSCs) that are induced by inoculation (immunization) with low virulence Candida species [i.e., Candida dubliniensis (Cd)] that infiltrate the bone marrow (BM). In contrast, more virulent Candida species (i.e., C. albicans), even at sub-lethal inocula, fail to induce similar levels of protection. The purpose of the present study was to test the hypothesis that the level of TII-mediated protection induced by Ca strains inversely correlates with damage in the BM as a reflection of virulence. Mice were immunized by intraperitoneal inoculation with several parental and mutant strains of C. albicans deficient in virulence factors (hyphal formation and candidalysin production), followed by an intraperitoneal Ca/Sa challenge 14 d later and monitored for sepsis and mortality. Whole femur bones were collected 24 h and 13 d after immunization and assessed for BM tissue/cellular damage via ferroptosis and histology. While immunization with standard but not sub-lethal inocula of most wild-type C. albicans strains resulted in considerable mortality, protection against lethal Ca/Sa IAI challenge varied by strain was usually less than that for C. dubliniensis, with no differences observed between parental and corresponding mutants. Finally, levels of protection afforded by the Ca strains were inversely correlated with BM tissue damage (R 2 = −0.773). TII-mediated protection against lethal Ca/Sa sepsis induced by Candida strain immunization inversely correlates with BM tissue/cellular damage as a reflection of localized virulence.
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影响因子：
10.1
作者：
Gabrilovich DI
通讯作者：
Gabrilovich DI
影响因子：
168.9
作者：
CALANDRA, T;SCHNEIDER, R;FRANCIOLI, P
通讯作者：
FRANCIOLI, P
影响因子：
4.1
作者：
Harry, Reese S.;Hiatt, Leslie A.;Wright, David W.
通讯作者：
Wright, David W.
DOI：
10.1007/s10096-013-1953-2
发表时间：
2014-02-01
影响因子：
4.5
作者：
Hwang, S. Y.;Yu, S. J.;Lee, H. -S.
通讯作者：
Lee, H. -S.
影响因子：
1.9
作者：
Karantonis, Fotios-Filippos;Nikiteas, Nikolaos;Kostakis, Alkiviadis
通讯作者：
Kostakis, Alkiviadis