Macrophages, CD4+ or CD8+ cells are each sufficient for protection against Chlamydia pneumoniae infection through their ability to secrete IFN-gamma.
By using a T, B, or NK cell-deficient mouse strain (recombinase-activating gene (RAG)-1(-/-)/common cytokine receptor gamma-chain (gamma(C)R)), and T and B cell and IFN-gamma-deficient (RAG-1(-/-)/IFN-gamma(-/-)) mice, we have studied the generation of immunity against infection by Chlamydia pneumoniae. We found that IFN-gamma secreted by innate-cell populations protect against C. pneumoniae infection. However, NK cells were not needed for such IFN-gamma-dependent innate immune protection. Inoculation of wild type, but not IFN-gamma(-/-) bone marrow-derived macrophages protected RAG-1(-/-)/IFN-gamma(-/-) mice against C. pneumoniae infection. In line, pulmonary macrophages from RAG-1(-/-) C. pneumoniae-infected mice expressed IFN-gamma mRNA. Reconstitution of RAG-1(-/-)/gamma(c)R(-/-) or RAG-1(-/-)/IFN-gamma(-/-) mice with CD4(+) or CD8(+) cells by i.v. transfer of FACS sorted wild type spleen cells (SC) increased resistance to C. pneumoniae infection. On the contrary, no protection was observed upon transfer of IFN-gamma(-/-) CD4(+) or IFN-gamma(-/-) CD8(+) SC. T cell-dependent protection against C. pneumoniae was weaker when IFN-gammaR(-/-) CD4(+) or IFN-gammaR(-/-) CD8(+) SC were inoculated into RAG-1(-/-)/IFN-gamma(-/-) mice. Thus both nonlymphoid and T cell-derived IFN-gamma can play a central and complementary role in protection against C. pneumoniae. IFN-gamma secreted by nonlymphoid cells was not required for T cell-mediated protection against C. pneumoniae; however, IFN-gamma regulated T cell protective functions.
Rothfuchs
Antonio Gigliotti
AG
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
Kreuger
Maria Regina
MR
Wigzell
Hans
H
Rottenberg
Martin E
ME
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D007371:Interferon-gamma