Tumor Necrosis Factor Alpha Receptor I Is Important for Survival fromStreptococcus pneumoniaeInfections

Abstract

Tumor necrosis factor alpha (TNF-α) is important in resistance to various microorganisms and provides signals to the target cells through two different receptors, TNF-α receptor I (TNFRI) (p55 receptor) and TNFRII (p75 receptor). To delineate the significance of the two different signaling pathways in resisting infections with extracellular bacteria, we examined the resistance of mice to Streptococcus pneumoniae (serotype 6B). TNF-α needs to be present early in infections, since one injection of wild-type mice with anti-TNF-α leads to an increased susceptibility of these mice to S. pneumoniae. TNF-α signaling through the p55 receptor (but not the p75 receptor) is crucial in resisting S. pneumoniae infections, because intraperitoneal injection of 100 CFU/mouse killed p55-deficient mice by day 2 of infection, whereas 1,000,000 CFU/mouse was needed to kill half of the control mice. p55-deficient mice do not show evidence of a deficient acute-phase response. All three types of mice (p55 deficient, p75 deficient, and normal) showed comparable rises in the levels of two acute-phase proteins (serum amyloid P and C3) at 24, 48, and 72 h after the experimental infections, and all of the mice showed comparable influxes of neutrophils to the site of infection. Finally, it was demonstrated that p55-deficient mice can be protected from the lethal effects of S. pneumoniae infection by injection of antibodies specific for S. pneumoniaepolysaccharide capsule.

Pneumococci: immunology of the innate host response

“…However, it appears that the overlapping effects of TNF‐α and IL‐1 are of central importance during the early stages of infection being responsible for enhancing cytokine expression, neutrophil recruitment and resultant bacterial killing via NFκB RelA activation 85–87 . The importance of TNF‐α during pneumococcal infection is substantiated in numerous experimental studies, 87–90 showing that deletion or neutralization of TNF‐α was detrimental and by the finding that human patients treated with anti‐TNF‐α therapies may have increased risk of invasive pneumococcal disease 91 . However, while protective, TNF‐α may also contribute to tissue damage and the upregulation of pneumococcal receptors such as during chronic low‐grade inflammation in the elderly 53,55 .…”

TNF: a moonlighting protein at the interface between cancer and infection

“…In most bacterial infection models, TNF-R1, rather than TNF-R2, was shown to be crucial for survival. Indeed, TNF-R1 -/mice were shown to be highly susceptible to infections with Listeria monocytogenes (83,84), Streptococcus pneumoniae (92) and with mycobacteria and other granulomatous pathogens, both in the active and latent phases of infection (84,93,94). Long-term neutralization of TNF activity in patients suffering from rheumatoid arthritis, in spite of excellent effects, can lead to reactivation of tuberculosis in a part of the patient population (95).…”

Impact of the myeloid Krüppel like factor4 during pneumococcal pneumonia

“…Additionally, TNF-α has also been found to play role in the adaptive immunity as literature review suggest that it is important for the production of B cellattracting chemokine-1 and secondary lymphoid tissue chemokine 127 . TNF-α has been reported to protect the host during pneumococcal infection 128,129 .…”