Prominent role for T cell-derived tumour necrosis factor for sustained control of Mycobacterium tuberculosis infection.

Nasiema Allie (1) , Sergei I Grivennikov (2, 3) , Roanne Keeton (1) , Nai-Jen Hsu (1) , Marie-Laure Bourigault (2) , Nathalie Court (2) , Cecile Fremond (2) , Vladimir Yeremeev (2) , Yuriy Shebzukhov (3, 4) , Bernhard Ryffel (2) , Sergei A Nedospasov (3, 4) , Valérie Quesniaux (2) , Muazzam Jacobs (1, 5)

1 IDM - Institute of Infectious Diseases and Molecular Medicine
2 INEM - Immunologie et Neurogénétique Expérimentales et Moléculaires
3 ISTC - Engelhardt Institute of Molecular Biology
4 Department of Inflammation, German Rheumatology Research Center
5 NHLS - National Health Laboratory Service

Tumour Necrosis Factor (TNF) is critical for host control of M. tuberculosis, but the relative contribution of TNF from innate and adaptive immune responses during tuberculosis infection is unclear. Myeloid versus T-cell-derived TNF function in tuberculosis was investigated using cell type-specific TNF deletion. Mice deficient for TNF expression in macrophages/neutrophils displayed early, transient susceptibility to M. tuberculosis but recruited activated, TNF-producing CD4(+) and CD8(+) T-cells and controlled chronic infection. Strikingly, deficient TNF expression in T-cells resulted in early control but susceptibility and eventual mortality during chronic infection with increased pulmonary pathology. TNF inactivation in both myeloid and T-cells rendered mice critically susceptible to infection with a phenotype resembling complete TNF deficient mice, indicating that myeloid and T-cells are the primary TNF sources collaborating for host control of tuberculosis. Thus, while TNF from myeloid cells mediates early immune function, T-cell derived TNF is essential to sustain protection during chronic tuberculosis infection.

Domaines: Immunologie

Nasiema Allie, Sergei I Grivennikov, Roanne Keeton, Nai-Jen Hsu, Marie-Laure Bourigault, et al.. Prominent role for T cell-derived tumour necrosis factor for sustained control of Mycobacterium tuberculosis infection.. Scientific Reports, 2013, 3, pp.1809. ⟨10.1038/srep01809⟩. ⟨hal-00941386⟩