Persistent p55TNFR expression impairs T cell responses during chronic tuberculosis and promotes reactivation

Ivy M. Dambuza, Roanne Keeton, Nai-Jen Hsu, Nasiema Allie, Valerie F. J. Quesniaux, Bernhard Ryffel, Muazzam Jacobs*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Citations (Scopus)
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Abstract

The pleiotropic activities of TNF are mediated by two structurally related but functionally distinct type I transmembrane receptors, p55TNFR and p75TNFR expressed in most cell types, that can be cleaved and act as TNF scavengers. Here, we investigated the effect of persistent p55TNFR cell surface expression during aerosol inhalation challenge with virulent M. tuberculosis H37Rv. We demonstrated that persistency of p55TNFR in macrophage cultures increased the synthesis of soluble TNF, p75TNFR and NO, however, had no effects on bacteria killing ability. Furthermore, it did not facilitate enhanced protection to primary acute M. tuberculosis infection in p55(Delta NS) mice. Without exacerbated lung inflammation, we found a compensatory increase in p75TNFR shedding and decrease in bioactive TNF in BAL of p55(Delta NS) mice after M. tuberculosis challenge. Defective expressions of CD44 and INF gamma attributed to an impaired T cell response during persistent p55TNFR expression that caused marginal transient susceptibility during chronic infection. Moreover, persistent p55TNFR expression induced early reactivation during latent tuberculosis infection. These data indicate a prominent role of p55TNFR shedding in Th1 mediated protection against chronic and latent tuberculosis infection.

Original languageEnglish
Article number39499
Number of pages17
JournalScientific Reports
Volume6
Early online date20 Dec 2016
DOIs
Publication statusPublished - 2016

Keywords

  • TUMOR-NECROSIS-FACTOR
  • FACTOR-BINDING-PROTEIN
  • FACTOR TNF RECEPTOR
  • FACTOR-ALPHA TNF
  • MYCOBACTERIUM-TUBERCULOSIS
  • GRANULOMA-FORMATION
  • DEFICIENT MICE
  • NITRIC-OXIDE
  • PERITONEAL-MACROPHAGES
  • PROTECTIVE IMMUNITY

Cite this

Dambuza, I. M., Keeton, R., Hsu, N-J., Allie, N., Quesniaux, V. F. J., Ryffel, B., & Jacobs, M. (2016). Persistent p55TNFR expression impairs T cell responses during chronic tuberculosis and promotes reactivation. Scientific Reports, 6, [39499]. https://doi.org/10.1038/srep39499