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 language | English |
|---|---|
| Article number | 39499 |
| Number of pages | 17 |
| Journal | Scientific Reports |
| Volume | 6 |
| Early online date | 20 Dec 2016 |
| DOIs | |
| Publication status | Published - 2016 |
Bibliographical note
AcknowledgementsWe thank Lizette Fick for her contribution to histopathology. We thank Faried Abbass for technical support. We thank the support staff of the Division of Immunology and the Research Animal Facility at the University of Cape Town for their contribution to animal care and technical support. The study was supported by the University of Cape Town, National Research Foundation (South Africa), South African Medical Research Council (SAMRC) National Health Laboratory Service (South Africa), The European Union (contract number: 028190), FP6 NEST project N°028190 “TB REACT”. Research carried out within the scope of the Franco/South African Laboratory “TB Immunity” (Associated International Laboratory ‘AIL’).
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
Access to Document
- Persistent p55TNFR expression impairs T cell responses during chronic tuberculosis and promotes reactivation
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/