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

doi:10.1038/srep39499

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

Applied Medicine

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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 language	English
Article number	39499
Number of pages	17
Journal	Scientific Reports
Volume	6
Early online date	20 Dec 2016
DOIs	https://doi.org/10.1038/srep39499
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Persistent p55TNFR expression impairs T cell responses during chronic tuberculosis and promotes reactivation
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@article{59320dd3cdf34198af38c2dd07392222,

title = "Persistent p55TNFR expression impairs T cell responses during chronic tuberculosis and promotes reactivation",

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.",

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",

author = "Dambuza, {Ivy M.} and Roanne Keeton and Nai-Jen Hsu and Nasiema Allie and Quesniaux, {Valerie F. J.} and Bernhard Ryffel and Muazzam Jacobs",

note = "Acknowledgements We 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 {\textquoteleft}AIL{\textquoteright}).",

year = "2016",

doi = "10.1038/srep39499",

language = "English",

volume = "6",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Persistent p55TNFR expression impairs T cell responses during chronic tuberculosis and promotes reactivation

AU - Dambuza, Ivy M.

AU - Keeton, Roanne

AU - Hsu, Nai-Jen

AU - Allie, Nasiema

AU - Quesniaux, Valerie F. J.

AU - Ryffel, Bernhard

AU - Jacobs, Muazzam

N1 - Acknowledgements We 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’).

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - TUMOR-NECROSIS-FACTOR

KW - FACTOR-BINDING-PROTEIN

KW - FACTOR TNF RECEPTOR

KW - FACTOR-ALPHA TNF

KW - MYCOBACTERIUM-TUBERCULOSIS

KW - GRANULOMA-FORMATION

KW - DEFICIENT MICE

KW - NITRIC-OXIDE

KW - PERITONEAL-MACROPHAGES

KW - PROTECTIVE IMMUNITY

U2 - 10.1038/srep39499

DO - 10.1038/srep39499

M3 - Article

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 39499

ER -

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

Abstract

Keywords

UN SDGs

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