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The meningeal lymphatic system: a route for HIV brain migration?

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Abstract

Two innovative studies recently identified functional lymphatic structures in the meninges that may influence the development of HIV-associated neurological disorders (HAND). Until now, blood vessels were assumed to be the sole transport system by which HIV-infected monocytes entered the brain by bypassing a potentially hostile blood-brain barrier through inflammatory-mediated semi-permeability. A cascade of specific chemokine signals promote monocyte migration from blood vessels to surrounding brain tissues via a well-supported endothelium, where the cells differentiate into tissue macrophages capable of productive HIV infection. Lymphatic vessels on the other hand are more loosely organized than blood vessels. They absorb interstitial fluid from bodily tissues where HIV may persist and exchange a variety of immune cells (CD4+ T cells, monocytes, macrophages, and dendritic cells) with surrounding tissues through discontinuous endothelial junctions. We propose that the newly discovered meningeal lymphatics are key to HIV migration among viral reservoirs and brain tissue during periods of undetectable plasma viral loads due to suppressive combinational antiretroviral therapy, thus redefining the migration process in terms of a blood-lymphatic transport system.

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Acknowledgments

MM, EM, CAS are funded by the National Cancer Institutes grant #CA181255. SLL, RR, MM are funded by the National Institutes of Mental Health grant #MH100984. SLL, DJN, MS are funded by the National Institutes of Neurological Disorders and Stroke grant #NS063897. LCH is funded by the National Institutes of Mental Health grant #MH104141

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Authors and Affiliations

  1. Bioinfoexperts, LLC, Thibodaux, LA, 70301, USA

    Susanna L. Lamers & Rebecca Rose

  2. University of Hawaii, Honolulu, HI, USA

    Lishomwa C. Ndhlovu

  3. University of Florida, Gainesville, FL, USA

    David J. Nolan & Marco Salemi

  4. University of California and the AIDS and Cancer Specimen Resource, San Francisco, CA, USA

    Ekaterina Maidji, Cheryl A. Stoddart & Michael S. McGrath

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  1. Susanna L. Lamers
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  2. Rebecca Rose
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Correspondence to Susanna L. Lamers.

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Lamers, S.L., Rose, R., Ndhlovu, L.C. et al. The meningeal lymphatic system: a route for HIV brain migration?. J. Neurovirol. 22, 275–281 (2016). https://doi.org/10.1007/s13365-015-0399-y

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