RESUMO
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.
Assuntos
Interferon gama/farmacologia , Ativação de Macrófagos/fisiologia , Macrófagos/imunologia , Receptores de Interferon/fisiologia , Animais , Bovinos , Linhagem Celular , Meios de Cultura , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Interferon beta/genética , Interleucinas/genética , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Polidesoxirribonucleotídeos/farmacologia , Receptores Imunológicos/efeitos dos fármacos , Receptores Imunológicos/fisiologia , Receptores de Interferon/efeitos dos fármacos , Receptores Depuradores , Proteínas Recombinantes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Soroalbumina Bovina/farmacologia , Ácidos Teicoicos/farmacologia , Fator de Necrose Tumoral alfa/genética , Receptor de Interferon gamaRESUMO
We localized peptide epitopes within the Chlamydia trachomatis (Ct) major outer membrane protein (MOMP) that activate human T cells. T-MOMP' cells were prepared by culturing PBL from 38 humans who had Ct infections in the presence of Ct serovar E MOMP. Some epitopes were first localized by quantifying proliferative responses of T-MOMP' cells to overlapping MOMP segments (sixths) that were produced in Escherichia coli. Further localization was achieved by using overlapping synthetic 16-22 mers that spanned stimulatory MOMP sixths as Ags. The APCs used were human B cell lines (LCL) that were matched or mismatched with respect to HLA class II alleles of the T-MOMP' cells. T cell epitopes were detected in 18 Ct serovar E MOMP 16-22 mers and were presented in association with HLA-DR1, -7, -13, -17, HLA-DRw52, HLA-DQ3 and at least two from among HLA-DR4, -8, -11, -14, -18, in probable addition to HLA-DP4. Peptide 249-265 stimulated T-MOMP' cells from 83% of the subjects; studies with overlapping 11-13 mers spanning peptide 249-265 revealed at least six epitopes presented with different HLA-class II allotypes. Diverse T-MOMP' cultures responded to between 2 and 7 MOMP epitopes. All but 1 of the 23 epitopes localized to date are distributed among four MOMP constant segments. T-MOMP' cells from subjects infected with serovars other than E also responded.
