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However, how <jats:italic>Mycobacterium tuberculosis<\/jats:italic> crosses the blood-brain barrier and how HIV-1 influences tuberculous meningitis pathogenesis remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Using human pericytes, astrocytes, endothelial cells, and microglia alone and combined in an in vitro blood-brain barrier model, we investigated the effect of <jats:italic>Mycobacterium tuberculosis<\/jats:italic> +\/- HIV-1 co-infection on central nervous system cell entry and function. Cells and the blood-brain barrier model were infected with <jats:italic>Mycobacterium tuberculosis<\/jats:italic> and\/or HIV-1 and we evaluated the effects of both infection on (i) cells susceptibility to <jats:italic>Mycobacterium tuberculosis<\/jats:italic> and its growth in cells by flow cytometry; (ii) modulation of blood-brain barrier permeability and <jats:italic>Mycobacterium tuberculosis<\/jats:italic> passage through it; (iii) viral and bacterial cytopathogenicity using the xCELLigence system; (iv) cell metabolic activity and ROS release using colorimetric assays; (v) extracellular glutamate concentration by fluorometric assay; (vi) the inflammatory response by Luminex; and (vii) endoplasmic reticulum stress by quantitative PCR.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We demonstrated that <jats:italic>Mycobacterium tuberculosis<\/jats:italic> infects and multiplies in all cell types with HIV-1 increasing entry to astrocytes and pericytes, and growth in HIV-1 positive pericytes and endothelial cells. <jats:italic>Mycobacterium<\/jats:italic>\n              <jats:italic> tuberculosis<\/jats:italic> also induces an increase of the blood-brain barrier permeability resulting in translocation of bacilli across it. Cytopathic effects include (i) increased markers of cellular stress (mitochondrial metabolic activity, unfolded protein response); (ii) ROS release; (iii) the induction of neurotoxic astrocytes; (iv) and the secretion of the excitotoxic neurotransmitter glutamate. Lastly, we observed distinct cell-type specific production of inflammatory and effector mediators.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>These results indicate that <jats:italic>Mycobacterium tuberculosis<\/jats:italic> can translocate the blood-brain barrier directly to initiate meningitis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12974-025-03467-7","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T16:53:36Z","timestamp":1748278416000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of M. tuberculosis and HIV-1 infection on in vitro blood-brain barrier function"],"prefix":"10.1186","volume":"22","author":[{"given":"Aliz\u00e9","family":"Proust","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin A.","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"3467_CR1","unstructured":"WHO. 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