Human Monocyte-Derived Macrophages (MDM): Model 2.

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.