HIV-1 and methamphetamine alter galectins -1, -3, and -9 in human monocyte-derived macrophages.

Kinga Grabowska,Pawel Ciborowski,Lubaba Zaman,Brenda Morsey,Katarzyna Macur,Sarah Zieschang,Nicole Haverland,Howard S Fox,Andrew Schissel

doi:10.1007/s13365-021-01025-4

Kinga Grabowska, Pawel Ciborowski + Show 7 more

Open Access

https://doi.org/10.1007/s13365-021-01025-4

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Abstract

Macrophages are key elements of the innate immune system. Their HIV-1 infection is a complex process that involves multiple interacting factors and various steps and is further altered by exposure of infected cells to methamphetamine (Meth), a common drug of abuse in people living with HIV. This is reflected by dynamic changes in the intracellular and secreted proteomes of these cells. Quantification of these changes poses a challenge for experimental design and associated analytics. In this study, we measured the effect of Meth on expression of intracellular and secreted galectins-1, -3, and -9 in HIV-1 infected human monocyte-derived macrophages (hMDM) using SWATH-MS, which was further followed by MRM targeted mass spectrometry validation. Cells were exposed to Meth either prior to or after infection. Our results are the first to perform comprehensive quantifications of galectins in primary hMDM cells during HIV-1 infection and Meth exposure a building foundation for future studies on the molecular mechanisms underlying cellular pathology of hMDM resulting from viral infection and a drug of abuse—Meth.Supplementary informationThe online version contains supplementary material available at 10.1007/s13365-021-01025-4.

Highlights

HIV-1 infection has devastating effects at various levels on the function of the entire organism (Niu et al 2020; Passaro et al 2015; Saito et al 2008)
Our main question in this study was the effect of Meth on already HIV-1-infected macrophages, and if such effect exists, how much macrophages are further altered in their intra- and extracellular metabolism
In addition to full unbiased profiling, we focused on galectins, both intracellular and secreted

Summary

Introduction

HIV-1 infection has devastating effects at various levels on the function of the entire organism (Niu et al 2020; Passaro et al 2015; Saito et al 2008). The macrophage (mononuclear phagocytes, MP), a key component of the innate immune system, is one of the prime targets of HIV-1 and a reservoir of productive viral infection constituting a vehicle to spread infection to organs. MPs survey their milieus and react to contain their pathological environment, including infections, or other sources of inflammation. Exposure to toxic substances, including Meth, impairs their protective capacities. It has been shown that HIV-1 infection results in changes in MP protein expression (Talloczy et al 2008); and the addition of Meth may further impact the functioning of the innate immune system (Kraft-Terry et al 2009)

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