Schistosoma mansoni egg-induced hepatic granulomas in mice deficient for the interferon-gamma receptor have altered populations of macrophages, lymphocytes and connective tissue cells.
Systemic production and mobilization of inflammatory cells and formation of hepatic periovular granulomas were studied in Schistosoma mansoni-infected mice with deficient interferon gamma (IFN-gamma) receptor (IFN-gammaR(o/o)). The impaired IFN-gamma signaling did not cause a significant modification of the overall kinetics of inflammatory cells, but mutant mice developed smaller hepatic periovular granulomas with a two-fold reduction in all the cell lineages. In granulomas of normal mice, the fully differentiated macrophages were progressively predominant, whilst in IFN-gammaR(o/o) mice, the granulomas contained a higher percentage of immature and proliferating monocytes. Granulomas of IFN-gammaR(o/o) mice had an enhanced and accelerated fibrotic reaction, corresponding to an increased content of proliferative and activated connective tissue cells. Simultaneously, their granulomas had an increased ratio of T over B cells, with an increase in CD8(+) and a reduction in CD4(+) T cells. The functional IFN-gamma receptor was not required for initial recruitment of monocytes and lymphocytes into granulomas, but it was necessary for the maturation of macrophages, upregulation of major histocompatibility class 2 (MHC-II) expression and consequent stimulation of lymphocyte subpopulations depending upon the MHC-II-mediated antigen presentation.
Oliveira
V R
VR
Ludwig Institute for Cancer Research, São Paulo, Brazil
El-Cheikh
M C
MC
Aguiar
A M
AM
Balduino
A
A
de Fátima B Pinho
M
M
Reis
L F
LF
Borojevic
R
R
D000818:Animals; D003239:Connective Tissue Cells / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D006099:Granuloma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008109:Liver Diseases, Parasitic / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012550:Schistosoma mansoni / Q000254:growth & development / Q000472:pathogenicity; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D000096743:Interferon gamma Receptor
D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor