Deficits in serum amyloid A contribute to increased neonatal mortality during murine listeriosis.

Abstract:

BACKGROUND:To understand the increased susceptibility of preterm neonates to infection. METHODS:A murine listeriosis model using immunohistochemistry, microarray technology, and real-time polymerase chain reaction (PCR). RESULTS:We report that recombinant serum amyloid A (SAA) administered prophylactically 18 h before intraperitoneal (i.p.) inoculation with Listeria monocytogenes conferred a dramatic survival benefit compared with administration of only vehicle in neonatal mice. Neonates that received the recombinant SAA protein had significantly fewer Listeria colony counts on plating of infected liver and showed significantly more activated macrophages, but SAA did not affect postnatal growth. Real-time PCR was used to confirm the microarray findings that gene expression levels for the SAA proteins 1 (Saa1) and 2 (Saa2), in addition to that for orosomucoid-2 (Orm2), were strikingly elevated in the adult compared with those in the neonate. Real-time PCR analysis showed that of the acute phase cytokines, tumor necrosis factor (TNF) gene expression increased exponentially with time in the infected adult, whereas neonates did not show similar increases. CONCLUSION:The increased susceptibility of neonatal mice to listeriosis is in part mediated by a deficiency in the acute phase response, specifically expression of SAA, and that prophylactic SAA protein before neonatal murine listeriosis results in more macrophage activation, lower Listeria counts, and greater survival.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Hawkins JS,Wu Q,Wang Y,Lu CY

doi

10.1038/pr.2013.164

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

668-74

issue

6

eissn

0031-3998

issn

1530-0447

pii

pr2013164

journal_volume

74

pub_type

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