Bordetella type III secretion modulates dendritic cell migration resulting in immunosuppression and bacterial persistence.
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-gamma production by restimulated splenocytes from infected animals. Wild-type bacteria also elicited peak IFN-gamma 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-gamma production that favors bacterial persistence.
Skinner
Jason A
JA
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Pilione
Mylisa R
MR
Shen
Hao
H
Harvill
Eric T
ET
Yuk
Ming H
MH
D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology; D001885:Bordetella Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D016950:Bordetella bronchiseptica / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D007165:Immunosuppression Therapy; D007370:Interferon Type I / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012141:Respiratory Tract Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D015854:Up-Regulation / Q000276:immunology
D001426:Bacterial Proteins; D007370:Interferon Type I; D016753:Interleukin-10