TY - JOUR
T1 - Rickettsiae stimulate dendritic cells through toll-like receptor 4, leading to enhanced NK cell activation in vivo
AU - Jordan, Jeffrey M.
AU - Woods, Michael E.
AU - Soong, Lynn
AU - Walker, David H.
N1 - Funding Information:
Received 6 June 2008; accepted 21 August 2008; electronically published 12 December 2008. Potential conflicts of interest: none reported. Presented in part: American Association of Immunologists Meeting, Miami, 18–22 May 2007 (abstract 44.14). Financial support: National Institute of Allergy and Infectious Diseases (grant AI21242 to D.H.W. and Emerging and Tropical Infectious Diseases Predoctoral Training Grant T32 AI007526 to J.M.J.); James W. McLaughlin Predoctoral Fellowship (J.M.J.). Reprints or correspondence: Dr. David Walker, Dept. of Pathology, Center for Biodefense and Emerging Infectious Diseases, 301 University Blvd., Galveston, TX 77555–0609 ([email protected]).
PY - 2009/1/15
Y1 - 2009/1/15
N2 - Adoptive transfer of Toll-like receptor (TLR) 4-stimulated dendritic cells (DCs) induces protective immunity against an ordinarily lethal rickettsial challenge, but the mechanism underlying this protection remains elusive. Therefore, we sought to determine the importance of TLR4 in early immunity to rickettsiae in vivo, particularly that conferred by TLR4-stimulated DCs. Rickettsial growth proceeded logarithmically in mice lacking TLR4 function, whereas in TLR4-competent mice rickettsial growth manifested a lag phase early, suggesting that TLR4 may initiate innate rickettsial immunity. TLR4-competent mice produced significant amounts of interferon (IFN)-γ on day 1 of Rickettsia conorii infection, which was associated with significant expansion of the population of activated NK cells. Moreover, NK cells from TLR4-competent mice produced significantly higher levels of IFN-γ and had greater cytotoxic activity than did those from TLR4-deficient mice. Last, adoptive transfer of rickettsiae-exposed, TLR4-stimulated DCs activated NK cells in vivo. Together, these data reveal an important role for DCs in recognizing rickettsiae through TLR4 and inducing early antirickettsial immunity.
AB - Adoptive transfer of Toll-like receptor (TLR) 4-stimulated dendritic cells (DCs) induces protective immunity against an ordinarily lethal rickettsial challenge, but the mechanism underlying this protection remains elusive. Therefore, we sought to determine the importance of TLR4 in early immunity to rickettsiae in vivo, particularly that conferred by TLR4-stimulated DCs. Rickettsial growth proceeded logarithmically in mice lacking TLR4 function, whereas in TLR4-competent mice rickettsial growth manifested a lag phase early, suggesting that TLR4 may initiate innate rickettsial immunity. TLR4-competent mice produced significant amounts of interferon (IFN)-γ on day 1 of Rickettsia conorii infection, which was associated with significant expansion of the population of activated NK cells. Moreover, NK cells from TLR4-competent mice produced significantly higher levels of IFN-γ and had greater cytotoxic activity than did those from TLR4-deficient mice. Last, adoptive transfer of rickettsiae-exposed, TLR4-stimulated DCs activated NK cells in vivo. Together, these data reveal an important role for DCs in recognizing rickettsiae through TLR4 and inducing early antirickettsial immunity.
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U2 - 10.1086/595833
DO - 10.1086/595833
M3 - Article
C2 - 19072551
AN - SCOPUS:58849133848
SN - 0022-1899
VL - 199
SP - 236
EP - 242
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -