Toll-like receptor 4 dependence of innate and adaptive immunity to Salmonella: importance of the Kupffer cell network.
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.
Vazquez-Torres
Andrés
A
Department of Microbiology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Vallance
Bruce A
BA
Bergman
Molly A
MA
Finlay
B Brett
BB
Cookson
Brad T
BT
Jones-Carson
Jessica
J
Fang
Ferric C
FC
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D019743:Chemokines, CXC / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D007728:Kupffer Cells / Q000276:immunology* / Q000473:pathology*; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D020297:Mice, Congenic; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D019779:Salmonella enterica / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D001426:Bacterial Proteins; D019743:Chemokines, CXC; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C075518:invA protein, Bacteria