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Flagellin enhances NK cell proliferation and activation directly and through dendritic cell‐NK cell interactions
Author(s) -
Tsujimoto Hironori,
Uchida Takefumi,
Efron Philip A.,
Scumpia Philip O.,
Verma Amrisha,
Matsumoto Tadashi,
Tschoeke Sven K.,
Ungaro Ricardo F.,
Ono Satoshi,
Seki Shuhji,
ClareSalzler Michael J.,
Baker Henry V.,
Mochizuki Hidetaka,
Ramphal Reuben,
Moldawer Lyle L.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0105051
Subject(s) - flagellin , tlr5 , biology , dendritic cell , t cell , myeloid , microbiology and biotechnology , immunology , innate immune system , toll like receptor , immune system , receptor , biochemistry
Flagellin, the principal component of bacterial flagella, is a ligand for Toll‐like receptor 5 (TLR5) or TLR11 and contributes to systemic inflammation during sepsis through activation of dendritic cells (DCs) and other cells of the innate immune system. Here, we report that flagellin and the TLR4 ligand, lipopolysaccharide (LPS), induced phenotypic and functional maturation of murine bone marrow‐derived DCs and enhanced DC accumulation in the draining popliteal lymph node following their footpad injection. It is interesting that flagellin injection enhanced myeloid (CD8α −1 ) and plasmacytoid (plasmacytoid DC antigen + B220 + ) DC subsets, whereas LPS only increased myeloid DCs in the draining lymph node. In addition, the footpad injection of flagellin or LPS induced significant CD4 + T cell activation in the draining popliteal lymph node, as judged by increased CD69 or CD25 expression. We illustrate, for the first time, that flagellin also increases natural killer (NK) cell number and activation status in the draining lymph node after footpad injection. Using coculture with enriched carboxy‐fluorescein diacetate succinimidyl ester‐labeled NK cells, flagellin‐treated DCs induce significant NK cell proliferation and activation. In fact, direct treatment of NK cells with flagellin induces a greater increase in cell proliferation than treatment with LPS. In contrast, flagellin treatment of NK cells was not a strong inducer of interferon‐γ (IFN‐γ) production, indicating that NK cell proliferation and IFN‐γ production may be regulated differentially. These data suggest that flagellin is a capable maturation agent for murine myeloid‐derived DCs, and flagellin‐activated DCs and flagellin itself are potent inducers of NK cell proliferation.