Benmerzoug, SMarinho, F.VRose, SMackowiak, CGosset, DSedda, DPoisson, EUyttenhove, CVan Snick, JJacobs, MGarcia, IRyffel, BQuesniaux, V.F.J2024-06-172024-06-172018-06-05Benmerzoug S, Marinho FV, Rose S, Mackowiak C, Gosset D, Sedda D, Poisson E, Uyttenhove C, Van Snick J, Jacobs M, Garcia I, Ryffel B, Quesniaux VFJ. GM-CSF targeted immunomodulation affects host response to M. tuberculosis infection. Sci Rep. 2018 Jun 5;8(1):8652. doi: 10.1038/s41598-018-26984-3.https://doi.org/10.1038/s41598-018-26984-3https://pubmed.ncbi.nlm.nih.gov/29872095/https://doi.org/10.1038/s41598-018-26984-3https://hdl.handle.net/11288/596592Host directed immunomodulation represents potential new adjuvant therapies in infectious diseases such as tuberculosis. Major cytokines like TNFα exert a multifold role in host control of mycobacterial infections. GM-CSF and its receptor are over-expressed during acute M. tuberculosis infection and we asked how GM-CSF neutralization might affect host response, both in immunocompetent and in immunocompromised TNFα-deficient mice. GM-CSF neutralizing antibodies, at a dose effectively preventing acute lung inflammation, did not affect M. tuberculosis bacterial burden, but increased the number of granuloma in wild-type mice. We next assessed whether GM-CSF neutralization might affect the control of M. tuberculosis by isoniazid/rifampicin chemotherapy. GM-CSF neutralization compromised the bacterial control under sub-optimal isoniazid/rifampicin treatment in TNFα-deficient mice, leading to exacerbated lung inflammation with necrotic granulomatous structures and high numbers of intracellular M. tuberculosis bacilli. In vitro, GM-CSF neutralization promoted M2 anti-inflammatory phenotype in M. bovis BCG infected macrophages, with reduced mycobactericidal NO production and higher intracellular M. bovis BCG burden. Thus, GM-CSF pathway overexpression during acute M. tuberculosis infection contributes to an efficient M1 response, and interfering with GM-CSF pathway in the course of infection may impair the host inflammatory response against M. tuberculosis.enAttribution 3.0 United Stateshttp://creativecommons.org/licenses/by/3.0/us/Mycobacterium tuberculosisAnimalsImmunomodulationImmunologic factorsSDG-03 Good health and well-beingArticleScientific Reports