TNF-α Compensates for the Impaired Host Defense of IL-1 Type I Receptor-Deficient Mice During Pneumococcal Pneumonia

Abstract

To determine the role of IL-1 in the host defense against pneumonia, IL-1R type I-deficient (IL-1R−/−) and wild-type (Wt) mice were intranasally inoculated with Streptococcus pneumoniae. Pneumonia resulted in elevated IL-1α and IL-1β mRNA and protein levels in the lungs. Survival rates did not differ between IL-1R−/− and Wt mice after inoculation with 5 × 104 or 2 × 105 CFU. At early time points (24 and 48 h) IL-1R−/− mice had 2-log more S. pneumoniae CFU in lungs than Wt mice; at 72 h bacterial outgrowth in lungs was similar in both groups. Upon histopathologic examination IL-1R−/− mice displayed a reduced capacity to form inflammatory infiltrates at 24 h after the induction of pneumonia. IL-1R−/− mice also had significantly less granulocyte influx in bronchoalveolar lavage fluid at 24 h after inoculation. Since TNF is known to enhance host defense during pneumonia, we determined the role of endogenous TNF in the early impairment and subsequent recovery of defense mechanisms in IL-1R−/− mice. All IL-1R−/− mice treated with anti-TNF rapidly died (no survivors (of 14 mice) after 4 days), while 10-day survival in IL-1R−/− mice (control Ab), Wt mice (anti-TNF), and Wt mice (control Ab) was 7 of 13, 3 of 14, and 12 of 13, respectively. These data suggest that TNF is more important for host defense against pneumococcal pneumonia than IL-1, and that the impaired early host defense in IL-1R−/− mice is compensated for by TNF at a later phase.

The Epidermal Growth Factor-Seven Transmembrane (EGF-TM7) Receptor CD97 Is Required for Neutrophil Migration and Host Defense

“…This assumption was tested in the well established S. pneumoniae pneumonia model (43)(44)(45). We first assessed the effect of the mAb 1B2 and 1C5 on survival of mice after i.n.…”

“…Pneumonia was induced as described previously (43)(44)(45). Briefly, S. pneumoniae serotype 3 was obtained from American Type Culture Collection (ATCC 6303; Rockville, MD).…”

Complement C1q and C3 Are Critical for the Innate Immune Response to Streptococcus pneumoniae in the Central Nervous System

“…In the preantibiotic era, pneumococcal meningitis was a lethal human disease, whereas the mortality rate for pneumococcal pneumonia was ϳ30 -35% (34,35). In experimental infection models, intracranial inoculation of 10 4 CFU/ml S. pneumoniae type 3 in C57BL/6 mice resulted in the death of all infected mice, whereas only one-quarter of mice died after intratracheal injection of an identical dose of the same strain (36,37). The bleak prognosis is closely related to the immune FIGURE 6.…”

Toll-Like Receptor 2 Plays a Role in the Early Inflammatory Response to Murine Pneumococcal Pneumonia but Does Not Contribute to Antibacterial Defense

“…Pneumonia was induced as described previously (23)(24)(25). Briefly, S. pneumoniae serotype 3 obtained from American Type Culture Collection (ATCC 6303; Manassas, VA) were grown for 6 h to midlogarithmic phase at 37°C using Todd-Hewitt broth (Difco, Detroit, MI), harvested by centrifugation at 1500 ϫ g for 15 min, and washed twice in sterile isotonic saline.…”

“…For this, the concentrations of TNF-␣, IL-1␤, IL-6, IL-10, KC, and MIP-2 were assessed in lung homogenates obtained from TLR2 Ϫ/Ϫ and wt mice 48 h after infection with a low (10 4 CFU), intermediate (approximate LD 60 ; 10 5 CFU), or high (lethal; 5 ϫ 10 5 CFU) S. pneumoniae dose. We chose to measure these mediators 48 h postinfection, because we previously established that this time point is suitable for this purpose in this model (23,24,29). Mediator levels did not differ between TLR2 Ϫ/Ϫ and wt mice (data not shown), except for KC and MIP-2 concentrations after infection with 10 5 S. pneumoniae CFU, which were lower in TLR2 Ϫ/Ϫ mice (1.6 Ϯ 0.5 and 8.3 Ϯ 2.1 ng/ml, respectively) than in wt mice (3.1 Ϯ 0.5 and 17.9 Ϯ 4.7 ng/ml, respectively; both p Յ 0.05 for the difference between groups).…”