TNF in host resistance to tuberculosis infection.
TNF is essential to control Mycobacterium tuberculosis infection and cannot be replaced by other proinflammatory cytokines. Overproduction of TNF may cause immunopathology, while defective TNF production results in uncontrolled infection. The critical role of TNF in the control of tuberculosis has been illustrated recently by primary and reactivation of latent infection in some patients under pharmacological anti-TNF therapy for rheumatoid arthritis or Crohn's disease. In this review, we discuss results of recent studies aimed at better understanding of molecular, cellular and kinetic aspects of TNF-mediated regulation of host-mycobacteria interactions. In particular, recent data using either mutant mice expressing solely membrane TNF or specific inhibitor sparing membrane TNF demonstrated that membrane TNF is sufficient to control acute M. tuberculosis infection. This is opening the way to selective TNF neutralization that might retain the desired anti-inflammatory effect but reduce the infectious risk.
Quesniaux
Valerie F J
VF
Molecular Immunology and Embryology UMR6218, Orleans University and CNRS, Orleans, France. quesniaux@cnrs-orleans.fr
Jacobs
Muazzam
M
Allie
Nasiema
N
Grivennikov
Sergei
S
Nedospasov
Sergei A
SA
Garcia
Irene
I
Olleros
Maria L
ML
Shebzukhov
Yuriy
Y
Kuprash
Dmitry
D
Vasseur
Virginie
V
Rose
Stephanie
S
Court
Nathalie
N
Vacher
Rachel
R
Ryffel
Bernhard
B
D000818:Animals; D057134:Antibodies, Neutralizing / Q000009:adverse effects; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D009169:Mycobacterium tuberculosis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
D057134:Antibodies, Neutralizing; D014409:Tumor Necrosis Factor-alpha