Enterobacter sakazakii targets DC-SIGN to induce immunosuppressive responses in dendritic cells by modulating MAPKs

Rahul Mittal, Silvia Bulgheresi, Claudia Emami, Nemani V. Prasadarao

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Enterobacter sakazakii (ES) is an emerging pathogen that causes meningitis and necrotizing enterocolitis in infants. Dendritic cells (DCs) are professional phagocytic cells that play an essential role in host defense against invading pathogens; however, the interaction of ES with DCs is not known. In this study, we demonstrate that ES targets DC-specific ICAM nonintegrin (DC-SIGN) to survive in myeloid DCs for which outer membrane protein A (OmpA) expression in ES is critical, although it is not required for uptake. In addition, DC-SIGN expression was sufficient to cause a significant invasion by ES in HeLa cells and intestinal epithelial cells, which are normally not invaded by ES. OmpA + ES prevented the maturation of DCs by triggering the production of high levels of IL-10 and TGF-β and by suppressing the activation of MAPKs. Pretreatment of DCs with Abs to IL-10 and TGF-β or of bacteria with anti-OmpA Abs significantly enhanced the maturation markers on DCs. Furthermore, DCs pretreated with various inhibitors of MAPKs prohibited the increased production of proinflammatory cytokines stimulated by LPS or OmpA- ES. LPS pretreatment followed by OmpA+ ES infection of DCs failed to induce maturation of DCs, indicating that OmpA+ ES renders the cells in immunosuppressive state to external stimuli. Similarly, OmpA+ ES-infected DCs failed to present Ag to T cells as indicated by the inability of T cells to proliferate in MLR. We conclude that ES interacts with DC-SIGN to subvert the host immune responses by disarming MAPK pathway in DCs.

Original languageEnglish (US)
Pages (from-to)6588-6599
Number of pages12
JournalJournal of Immunology
Volume183
Issue number10
DOIs
StatePublished - Nov 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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