The contribution of dendritic cells to host defenses against Streptococcus pyogenes.
BACKGROUND
Infection with Streptococcus pyogenes remains a significant health care problem. The identification of immune components required for host defenses against S. pyogenes constitutes an important area of research.


METHODS
Here, we have investigated the role played by dendritic cells (DCs) during infection with S. pyogenes by use of a murine infection model.


RESULTS
Our results show that S. pyogenes induced the maturation of murine DCs, which involved the up-regulation of CD40, CD80, CD86, and major histocompatibility complex class II molecules and the production of interleukin (IL)-12 and tumor necrosis factor-alpha. After subcutaneous infection of mice, S. pyogenes disseminated systemically via the draining lymph nodes. The contribution of DCs to bacterial dissemination was negligible, because most microorganisms were found free in lymph nodes. The contribution of DCs to host defenses against S. pyogenes was investigated using CD11c-diphtheria toxin (DT) receptor (DTR) transgenic mice, in which CD11c(high) cells (conventional DCs) can be transiently depleted in vivo by treatment with low doses of DT. We show that ablation of DCs led to increased bacterial dissemination into draining lymph nodes and systemic organs. Furthermore, ablation of DCs abolished IL-12 production, which is required for effective control of infection.


CONCLUSIONS
These data demonstrate that DCs contribute to host defenses against S. pyogenes, likely through the production of IL-12.
Loof
Torsten G
TG
Infection Immunology Research Group and Department of Microbial Pathogenesis, Helmholtz Center for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Rohde
Manfred
M
Chhatwal
Gursharan S
GS
Jung
Steffen
S
Medina
Eva
E
D000818:Animals; D039521:CD11c Antigen / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D066257:Heparin-binding EGF-like Growth Factor; D007279:Injections, Subcutaneous / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D039521:CD11c Antigen; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12