Analysis of interferon-gamma-dependent and -independent pathways of macrophage activation.
Macrophages are a cellular cornerstone of the innate immune response. The outcome of macrophage activity during development of an immune response to microbes results from macrophage activation by both organism-derived and host-derived factors. In order to more fully understand the spectrum of responses expressed by macrophages when encountering these distinct stimuli, we investigated the similarities and differences between interferon-gamma receptor (IFN-gammaR)-dependent macrophage activation and stimulation of macrophages through the Type A1 scavenger receptor (SR). We observed distinct patterns of macrophage activation depending on the nature of the ligand. IFN-gamma and the SR ligand lipotechoic acid (LTA) induced largely non-overlapping sets of genes. The use of two additional SR ligands, maleylated bovine serum albumin and the polydeoxynucleotide poly dI:dC, revealed differences within SR activation-induced gene expression. We also observed that priming with IFN-gamma resulted in an enhanced response to subsequent SR-mediated activation. These results suggest that full potentiation of macrophage activity during development of an antimicrobial immune response is achieved by activation of these cells through multiple receptors.
Paulnock
D M
DM
Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison 53706-1532, USA. paulnock@facstaff.wisc.edu
Demick
K P
KP
Coller
S P
SP
D000818:Animals; D002417:Cattle; D002460:Cell Line; D003470:Culture Media; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D016899:Interferon-beta / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology*; D007378:Interleukins / Q000235:genetics; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D011089:Polydeoxyribonucleotides / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000187:drug effects / Q000502:physiology; D017471:Receptors, Interferon / Q000187:drug effects / Q000502:physiology*; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013682:Teichoic Acids / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000096743:Interferon gamma Receptor
D003470:Culture Media; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016899:Interferon-beta; D007371:Interferon-gamma; D007378:Interleukins; D011089:Polydeoxyribonucleotides; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; D012710:Serum Albumin, Bovine; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor; C049877:maleylalbumin; C031156:poly d(I-C)