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Activated CD4 T cells in tuberculosis express OX40, a target for host-directed immunotherapy [Tetramer_scRNASeq]

ABSTRACT: Define genes expressed by CD4 T cells in the lungs of Mycobacterium tuberculosis-infected mice

ORGANISM(S): Mus musculus

PROVIDER: GSE235563 | GEO | 2023/11/06

REPOSITORIES: GEO

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Project description:Despite substantial investments, tuberculosis remains one of the biggest challenges in public health. DNA-immunotherapy is increasingly being suggested as a possibility to assist conventional treatment of tuberculosis. This strategy could allow treatment to be more efficient, faster and with advantages and modulate the host immune response, as demonstrated by our group with DNAhsp65 vaccine (Silva, Bonato et al., Gene Therapy, 2005). Based on this evidences, we performed a microarray assay to stydy the functional effects of DNAhsp65 immunotherapy associated with conventional chemotherapy in murine experimental tuberculosis. Briefly, we used a murine model of tuberculosis treatment compost by DNAhsp65 vaccine, or rifampicin and isoniazid or both therapies combined and performed a comprehensive analysis of its effects on gene expression of hostM-bM-^@M-^Ys lung . Female BALB/c mice,8 weeks old, were inoculated with 1.0 M-CM-^W 10e5 viable bacilli of Mycobacterium tuberculosis H37Rv strain by the intra-tracheal route in a level III bio-safety room facility (day 0). They were segregated in four groups, described below, with three animals each one. Control M-bM-^@M-^S just infected and not treated. Immunotherapy - Thirty days after challenge, 50 M-NM-<g of plasmid with DNA-insert (DNAhsp65) was administered by intramuscular injection in 50 M-NM-<L of 25% saccharose solution in saline into each quadriceps muscle, in four occasions, and at 10-days intervals, performing a final dose of 400 M-NM-<g of plasmid DNAhsp65 per animal. Control infected mice received saline. Chemotherapy - Thirty days after infection, animals were treated with water solution of isoniazid (25 mg/Kg, Sigma-Aldrich, St. Louis, MO, USA) and rifampicin (20 mg/Kg, Sigma-Aldrich, St. Louis, MO, USA) daily, during 30 days, by gavage. Control infected mice received the same volume of water. Association - The therapeutical association consists of the both therapeutical approaches, as described above. Ten days after the end of treatments, mice were killed by cervical dislocation under mild anesthesia, and lungs were removed to RNA extraction.

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Activated CD4 T cells in tuberculosis express OX40, a target for host-directed immunotherapy [Tetramer_scRNASeq]

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