Regulation and role of IFN-gamma in the innate resistance to infection with Chlamydia pneumoniae.
By using mice genomically lacking IFN-gammaR, IL-12, perforin, and recombination-activating gene-1 (RAG-1), we analyzed the regulation and importance of IFN-gamma in the control of infection with Chlamydia pneumoniae. IL-12 participates in resistance of mice to C. pneumoniae, probably by regulating the protective levels of IFN-gamma mRNA. In turn, IFN-gamma is necessary for the increased IL-12p40 mRNA accumulation that occurs in lungs during infection with C. pneumoniae, suggesting a positive feedback regulation between these two cytokines. In experiments including RAG-1-/-/IFN-gammaR-/- mice we showed that IFN-gamma produced by innate cells controls the bacterial load and is necessary for the increased accumulation of transcripts for enzymes controlling high output NO release (inducible NO synthase), superoxide production (gp-91 NADPH oxidase), and catalysis of tryptophan (indoleamine 2, 3-dioxygenase (IDO)), mechanisms probably related to bacterial killing. Adaptive immune responses diminish the levels of IFN-gamma and IL-12 mRNA and thereby the levels of inducible NO synthase, IDO, and gp91 NADPH oxidase transcripts. By using RAG-1-/-/perforin-/- mice, we excluded the overt participation of NK cell cytotoxicity in the control of C. pneumoniae. However, NK cells and probably other innate immune cells release IFN-gamma during the bacterial infection.
Rottenberg
M E
ME
Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden. Martin.Rottenberg@mtc.ki.se
Gigliotti Rothfuchs
A
A
Gigliotti
D
D
Ceausu
M
M
Une
C
C
Levitsky
V
V
Wigzell
H
H
D000818:Animals; D002690:Chlamydia Infections / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005677:G(M1) Ganglioside / Q000276:immunology; D016654:Genes, RAG-1 / Q000276:immunology; D020022:Genetic Predisposition to Disease; D007106:Immune Sera / Q000008:administration & dosage; D007113:Immunity, Innate / Q000235:genetics; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000235:genetics; D017384:Sequence Deletion; D000096743:Interferon gamma Receptor
D005677:G(M1) Ganglioside; D007106:Immune Sera; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C018835:asialo GM1 ganglioside