2023,
Infection and Immunity.
DOI:
10.1128/iai.00252-23
Protection against lethal sepsis following immunization with <i>Candida</i> species varies by isolate and inversely correlates with bone marrow tissue damage
Elizabeth A. Lilly, Breah E. Bender, Mairi C. Noverr, Paul L. Fidel
Abstract:
ABSTRACT
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.
Protection against lethal
(
)/
(
) 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
species [i.e.,
(
)] that infiltrate the bone marrow (BM). In contrast, more virulent
species (i.e.,
), 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
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
deficient in virulence factors (hyphal formation and candidalysin production), followed by an intraperitoneal
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
strains resulted in considerable mortality, protection against lethal
/
IAI challenge varied by strain was usually less than that for
, with no differences observed between parental and corresponding mutants. Finally, levels of protection afforded by the
strains were inversely correlated with BM tissue damage (
= −0.773). TII-mediated protection against lethal
sepsis induced by
strain immunization inversely correlates with BM tissue/cellular damage as a reflection of localized virulence.
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2023-09-29 22:03:00
钟鸣:
#paper doi：10.1128/iai.00252-23 Protection against lethal sepsis following immunization with Candida species varies by isolate and inversely correlates with bone marrow tissue damage 文章通过攻毒保护实验探讨了不同念珠菌接种小鼠后引发的免疫保护能力。结果认为，不同毒力表型的分离株提供的保护作用各不相同，不提供交叉保护。第二，股骨组织的铁死亡和结构完整性可作为定量指标衡量分离株的毒力强弱。此外还有一个意料之外的现象：毒力最强的分离株提供的免疫保护作用却最弱。