Abstract
Monocytes are key modulators in acute viral infections, determining both inflammation and development of specific B- and T-cell responses. Recently, these cells were shown to be associated to different SARS-CoV-2 infection outcome. However, their role in acute HIV-1 infection remains unclear. We had the opportunity to evaluate the mononuclear cell compartment in an early hyper-acute HIV-1 patient in comparison with an untreated chronic HIV-1 and a cohort of SARS-CoV-2 infected patients, by high dimensional flow cytometry using an unsupervised approach. A distinct polarization of the monocyte phenotype was observed in the two viral infections, with maintenance of pro-inflammatory M1-like profile in HIV-1, in contrast to the M2-like immunosuppressive shift in SARS-CoV-2. Noticeably, both acute infections had reduced CD14low/−CD16+ non-classical monocytes, with depletion of the population expressing Slan (6-sulfo LacNac), which is thought to contribute to immune surveillance through pro-inflammatory properties. This depletion indicates a potential role of these cells in acute viral infection, which has not previously been explored. The inflammatory state accompanied by the depletion of Slan+ monocytes may provide new insights on the critical events that determine the rate of viral set-point in acute HIV-1 infection and subsequent impact on transmission and reservoir establishment.
Highlights
The introduction of combined antiretroviral therapy, in 1996, dramatically changed the prognosis of HIV-1 infection, but soon it was realized the need of complementary approaches to control viral persistency
We enrolled 11 healthy subjects and a treatment naïve chronic HIV-1 patient, asymptomatic despite an advanced disease stage as illustrated by the low CD4+ T-cell count (Table 1). Both the acute HIV-1- and SARS-CoV-2-infected patients showed signs of inflammation, namely elevated C reactive protein (CRP) and ferritin levels, as expected in an acute viral infection, though IL-6 was only elevated in SARS-CoV-2-infected patients
COVID-19 was associated with neutrophilia with lymphopenia, as reported before [3], which was not observed in the acute HIV-1-infected patient (Table 1)
Summary
The introduction of combined antiretroviral therapy (cART), in 1996, dramatically changed the prognosis of HIV-1 infection, but soon it was realized the need of complementary approaches to control viral persistency. HIV-1 infection reduces the viral set-point and immune-activation, it does not prevent the establishment of cell reservoirs of integrated provirus [1]. The inflammatory environment is determinant for the dissemination and the establishment of HIV-1 infection, and monocytes are central in these processes [2]. Monocyte responses have been emerging as main contributors for the pathogenesis of another acute infection, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [3]. Monocyte responses have been emerging as main contributors for the pathogenesis of another acute infection, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [3]. 4.0/).
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