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Title: Expression and Function of S100A8/A9 (Calprotectin) in Human Typhoid Fever and the Murine Salmonella Model
Authors: Hanna K. De Jong
Ahmed Achouiti
Gavin C.K.W. Koh
Christopher M. Parry
Stephen Baker
Mohammed Abul Faiz
Jaap T. van Dissel
Albert M. Vollaard
Ester M.M. van Leeuwen
Joris J.T.H. Roelofs
Alex F. de Vos
Johannes Roth
Tom van der Poll
Thomas Vogl
Willem Joost Wiersinga
Academic Medical Centre, University of Amsterdam
University of Cambridge
Mahidol University
Churchill Hospital
Liverpool School of Tropical Medicine
Oxford University Clinical Research Unit (OUCRU)
Chittagong Medical College Hospital
Leiden University Medical Center - LUMC
Westfalische Wilhelms-Universitat Munster
Keywords: Medicine
Issue Date: 10-Apr-2015
Citation: PLoS Neglected Tropical Diseases. Vol.9, No.4 (2015)
Abstract: © 2015 De Jong et al. Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model. S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT) and S100A9-/-mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/-mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury. S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response against S. Typhimurium in mice.
ISSN: 19352735
Appears in Collections:Scopus 2011-2015

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