Abstract
In addition to CD4+ T cells, tissue-resident macrophages are target of productive HIV-1 infection. Unlike CD4+ T lymphocytes they are characterized by a substantial resistance to the cytopathic effects triggered by viral infection. This feature, in addition to their homeostatic self-renewal capacity, strongly support the hypothesis that macrophages could serve as an additional reservoir of persistently infected cells in individuals receiving combination antiretroviral therapy (cART).
In order to study the peculiar aspects of HIV-1 infection of macrophages, human primary monocyte-derived macrophages (MDM) represent the most exploited model given the difficulty to obtain and maintain in culture for significant periods of time macrophages from different organs and tissues. Here we present a model of MDM differentiation achieved in the absence of addition of exogenous cytokines (such as GM-CSF, discussed in the previous chapter), that could be further investigated in term of cell polarization toward classic, proinflammatory “M1”, or alternatively activated “M2” cells before or after infection. We will also discuss how to reinforce the M1-polarization protocol to obtain a reliable model of reversible latency of infectious HIV-1 in primary M1-MDM.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Joseph SB, Lee B, Swanstrom R (2014) Affinofile assay for identifying macrophage-tropic HIV-1. Bio Protoc 4(14):e1184. https://doi.org/10.21769/BioProtoc.1184
International ASSWGoHIVC, Deeks SG, Autran B, Berkhout B, Benkirane M, Cairns S, Chomont N, Chun TW, Churchill M, Di Mascio M, Katlama C, Lafeuillade A, Landay A, Lederman M, Lewin SR, Maldarelli F, Margolis D, Markowitz M, Martinez-Picado J, Mullins JI, Mellors J, Moreno S, O'Doherty U, Palmer S, Penicaud MC, Peterlin M, Poli G, Routy JP, Rouzioux C, Silvestri G, Stevenson M, Telenti A, Van Lint C, Verdin E, Woolfrey A, Zaia J, Barre-Sinoussi F (2012) Towards an HIV cure: a global scientific strategy. Nat Rev Immunol 12(8):607–614. https://doi.org/10.1038/nri3262
Sreejit G, Fleetwood AJ, Murphy AJ, Nagareddy PR (2020) Origins and diversity of macrophages in health and disease. Clin Transl Immunol 9(12):e1222. https://doi.org/10.1002/cti2.1222
Honeycutt JB, Garcia JV (2018) Humanized mice: models for evaluating NeuroHIV and cure strategies. J Neurovirol 24(2):185–191. https://doi.org/10.1007/s13365-017-0567-3
Abreu C, Shirk EN, Queen SE, Beck SE, Mangus LM, Pate KAM, Mankowski JL, Gama L, Clements JE (2019) Brain macrophages harbor latent, infectious simian immunodeficiency virus. AIDS 33(Suppl 2):S181–S188. https://doi.org/10.1097/QAD.0000000000002269
Cassol E, Cassetta L, Rizzi C, Alfano M, Poli G (2009) M1 and M2a polarization of human monocyte-derived macrophages inhibits HIV-1 replication by distinct mechanisms. J Immunol 182(10):6237–6246. https://doi.org/10.4049/jimmunol.0803447
Graziano F, Aimola G, Forlani G, Turrini F, Accolla RS, Vicenzi E, Poli G (2018) Reversible human immunodeficiency virus Type-1 latency in primary human monocyte-derived macrophages induced by sustained M1 polarization. Sci Rep 8(1):14249. https://doi.org/10.1038/s41598-018-32451-w
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Graziano, F., Vicenzi, E., Poli, G. (2022). Human Monocyte-Derived Macrophages (MDM): Model 2. In: Poli, G., Vicenzi, E., Romerio, F. (eds) HIV Reservoirs. Methods in Molecular Biology, vol 2407. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1871-4_9
Download citation
DOI: https://doi.org/10.1007/978-1-0716-1871-4_9
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-1870-7
Online ISBN: 978-1-0716-1871-4
eBook Packages: Springer Protocols