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4-week mouse comparative study on effect of neutralizing IL-17A, IL-17F and TNFa antibodies

ABSTRACT: Molecular profiling of effect of TNFα neutralization in contrast to anti-IL-17A or anti-IL-17F treatment for 28 days in lungs of M. tuberculosis infected C57BL/6 mice. Animals were treated once per week (starting day-1) with anti-mouse IL-17A or IL-17F antibodies (20 mg/kg i.p.), anti-mouse TNFα antibody (10 mg/kg), respective isotype control antibodies. Moreover, infected and non-infected TNFα-deficient mice were also analysed. Gene expression data revealed major changes of inflammatory and immune gene expression signatures 4 weeks post-infection (including host-pathogen interactions, macrophage recruitment, activation and polarization, host-anti-mycobacterial activities, immunomodulatory responses and extracellular matrix metallopeptidases) after TNFα blockade, while IL-17A or IL-17F neutralization elicited only mild changes of few genes without impaired host resistance four weeks after M. tuberculosis infection.

ORGANISM(S): Mus musculus

SUBMITTER: Elaine Tritto 

PROVIDER: E-MTAB-5218 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Controlled Mycobacterium tuberculosis infection in mice under treatment with anti-IL-17A or IL-17F antibodies, in contrast to TNFα neutralization.

Segueni Noria N   Tritto Elaine E   Bourigault Marie-Laure ML   Rose Stéphanie S   Erard François F   Le Bert Marc M   Jacobs Muazzam M   Di Padova Franco F   Stiehl Daniel P DP   Moulin Pierre P   Brees Dominique D   Chibout Salah-Dine SD   Ryffel Bernhard B   Kammüller Michael M   Quesniaux Valerie F VF  

Scientific reports 20161117

Antibodies targeting IL-17A or its receptor IL-17RA show unprecedented efficacy in the treatment of autoimmune diseases such as psoriasis. These therapies, by neutralizing critical mediators of immunity, may increase susceptibility to infections. Here, we compared the effect of antibodies neutralizing IL-17A, IL-17F or TNFα on murine host responses to Mycobacterium tuberculosis infection by evaluating lung transcriptomic, microbiological and histological analyses. Coinciding with a significant i  ...[more]

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