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Πέμπτη 19 Οκτωβρίου 2017

ADJUVANT PRETREATMENT WITH ALUM PROTECTS NEONATAL MICE IN SEPSIS THROUGH MYELOID CELL ACTIVATION

ABSTRACT

The high mortality in neonatal sepsis has been related to both quantitative and qualitative differences in host protective immunity. Especially in the premature neonate where outcomes from sepsis are so dismal, pretreatment strategies to prevent sepsis have received inadequate consideration. Aluminum-based adjuvants (alum) are currently used in many pediatric vaccines, but their use as an innate immune stimulant alone has not been well studied. We asked whether pre-treatment with alum adjuvant alone could improve outcome and host innate immunity in neonatal mice given polymicrobial sepsis. Subcutaneous alum pretreatment improves survival to polymicrobial sepsis in both wild-type, and in T- and B- cell-deficient neonatal mice, but not in caspase-1/11 null mice. Moreover, alum increases peritoneal macrophage and neutrophil phagocytosis, and decreases bacterial colonization in the peritoneum. Bone marrow-derived neutrophils from alum-pretreated neonates produce more extracellular traps (NETs), and exhibit increased expression of neutrophil elastase (NE) after in vitro stimulation with phorbol esters. In addition, alum pretreatment increases bone marrow and splenic hematopoietic stem cell expansion following sepsis. Pretreatment of neonatal mice with an alum-based adjuvant can stimulate multiple innate immune cell functions, and improve survival. These novel findings suggest a therapeutic pathway for the use of existing alum-based adjuvants for preventing sepsis in premature infants. This article is protected by copyright. All rights reserved.



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