Roles of interleukin-12 and gamma interferon in murine Chlamydia pneumoniae infection.
BALB/c and strain 129 mice infected intranasally with Chlamydia pneumoniae displayed a moderate-to-severe inflammation in the lungs and produced interleukin-12 (IL-12), gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and IL-10, with peak levels on days 1 to 3 postinfection (p.i.), returning to basal levels by day 16 p.i. Anti-IL-12 treatment resulted in less-severe pathological changes but higher bacterial titers on days 3 and 7 p.i. By day 16 p.i., the inflammatory responses of control antibody-treated mice subsided. The bacterial titers of both anti-IL-12- and control antibody-treated mice decreased within 3 weeks to marginally detectable levels. Anti-IL-12 treatment significantly reduced lung IFN-gamma production and in vitro spleen cell IFN-gamma production in response to either C. pneumoniae or concanavalin A. In gamma-irradiated infected mice, cytokine production was delayed, and this delay correlated with high bacterial titers in the lungs. Following C. pneumoniae infection, 129 mice lacking the IFN-gamma receptor alpha chain gene (G129 mice) produced similar IL-12 levels and exhibited similarly severe pathological changes but had higher bacterial titers than 129 mice. However, by day 45 p.i., bacterial titers became undetectable in both wild-type 129 and G129 mice. Thus, during C. pneumoniae lung infection, IL-12, more than IFN-gamma, plays a role in pulmonary-cell infiltration. IFN-gamma and IL-12, acting mostly through its induction of IFN-gamma and Th1 responses, play an important role in controlling acute C. pneumoniae infection in the lungs, but eventually all mice control the infection to undetectable levels by IL-12- and IFN-gamma-independent mechanisms.
Geng
Y
Y
The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104, USA.
Berencsi
K
K
Gyulai
Z
Z
Valyi-Nagy
T
T
Gonczol
E
E
Trinchieri
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002690:Chlamydia Infections / Q000276:immunology*; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D007165:Immunosuppression Therapy; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology* / Q000502:physiology*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology* / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017471:Receptors, Interferon / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000096743:Interferon gamma Receptor
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007371:Interferon-gamma; D016753:Interleukin-10; D018664:Interleukin-12; D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor