Bordetella type III secretion modulates dendritic cell migration resulting in immunosuppression and bacterial persistence

Jason A. Skinner, Mylisa R. Pilione, Hao Shen, Eric T. Harvill, Ming H. Yuk

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Chronic bacterial infection reflects a balance between the host immune response and bacterial factors that promote colonization and immune evasion. Bordetella bronchiseptica uses a type III secretion system (TTSS) to persist in the lower respiratory tract of mice. We hypothesize that colonization is facilitated by bacteria-driven modulation of dendritic cells (DCs), which leads to an immunosuppressive adaptive host response. Migration of DCs to the draining lymph nodes of the respiratory tract was significantly increased in mice infected with wild-type B. bronchiseptica compared with mice infected with TTSS mutant bacteria. Reduced colonization by TTSS-deficient bacteria was evident by 7 days after infection, whereas colonization by wild-type bacteria remained high. This decrease in colonization correlated with peak IFN-γ production by restimulated splenocytes from infected animals. Wild-type bacteria also elicited peak IFN-γ production on day 7, but the quantity was significantly lower than that elicited by TTSS mutant bacteria. Additionally, wild-type bacteria elicited higher levels of the immunosuppressive cytokine IL-10 compared with the TTSS mutant bacteria. B. bronchiseptica colonization in IL-10-/- mice was significantly reduced compared with infections in wild-type mice. These findings suggest that B. bronchiseptica use the TTSS to rapidly drive respiratory DCs to secondary lymphoid tissues where these APCs stimulate an immunosuppressive response characterized by increased IL-10 and decreased IFN-γ production that favors bacterial persistence.

Original languageEnglish (US)
Pages (from-to)4647-4652
Number of pages6
JournalJournal of Immunology
Volume175
Issue number7
DOIs
StatePublished - Oct 1 2005

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Bordetella type III secretion modulates dendritic cell migration resulting in immunosuppression and bacterial persistence'. Together they form a unique fingerprint.

Cite this