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Toll-like receptor 4 dependence of innate and adaptive immunity to Salmonella: importance of the Kupffer cell network.
Title | Toll-like receptor 4 dependence of innate and adaptive immunity to Salmonella: importance of the Kupffer cell network. |
Publication Type | Journal Article |
Year of Publication | 2004 |
Authors | Vazquez-Torres, A, Vallance, BA, Bergman, MA, B Finlay, B, Cookson, BT, Jones-Carson, J, Fang, FC |
Journal | J Immunol |
Volume | 172 |
Issue | 10 |
Pagination | 6202-8 |
Date Published | 2004 May 15 |
ISSN | 0022-1767 |
Keywords | Animals, Bacterial Proteins, Chemokines, CXC, Cytotoxicity, Immunologic, Genetic Predisposition to Disease, Immunity, Innate, Kupffer Cells, Liver, Macrophages, Peritoneal, Membrane Glycoproteins, Mice, Mice, Congenic, Mice, Inbred C3H, Mice, Knockout, Neutrophil Infiltration, Phagocytosis, Receptors, Cell Surface, Salmonella enterica, Salmonella Infections, Animal, Signal Transduction, Toll-Like Receptor 4, Toll-Like Receptors |
Abstract | Mammalian cells recognize LPS from Gram-negative bacteria via the Toll-like receptor 4 (TLR4) complex. During experimental Salmonella infection, C3H/HeJ mice carrying a dominant-negative mutation in TLR4 exhibited delayed chemokine production, impaired NO generation, and attenuated cellular immune responses. However, dramatically enhanced bacterial growth within the Kupffer cell network before the recruitment of inflammatory cells appeared to be primarily responsible for the early demise of Salmonella-infected TLR4-deficient mice. LPS-TLR4 signaling plays an essential role in the generation of both innate and adaptive immune responses throughout the course of infection with Gram-negative bacteria. Alternative pattern-recognition receptors cannot completely compensate for the loss of TLR4, and compensation occurs at the expense of an increased microbial burden. |
Alternate Journal | J. Immunol. |
PubMed ID | 15128808 |
Grant List | AI10181 / AI / NIAID NIH HHS / United States AI39557 / AI / NIAID NIH HHS / United States AI47242 / AI / NIAID NIH HHS / United States AI54959 / AI / NIAID NIH HHS / United States RR16082 / RR / NCRR NIH HHS / United States |