Abstract
While antiretroviral therapy increases the longevity of people living with HIV (PLWH), about 30% of this population suffers from three or more concurrent comorbidities, whose mechanisms are not well understood. Chronic activation and dysfunction of the immune system could be one potential cause of these comorbidities. We recently demonstrated reduced macrophage infiltration and delayed resolution of inflammation in the lungs of HIV-transgenic mice. Additionally, trans-endothelial migration of HIV-positive macrophages was reduced in vitro. Here, we analyze macrophages’ response to LPS challenge in the kidney and peritoneum of HIV-Tg mice. In contrast to the lung infiltration, renal and peritoneal macrophage infiltrations were similar in WT and HIV-Tg mice. Higher levels of HIV-1 gene expression were detected in lung macrophages compared to peritoneal macrophages. In peritoneal macrophages, HIV-1 gene expression was increased when they were cultured at 21% O2 compared to 5% O2, inversely correlating with reduced trans-endothelial migration at higher oxygen levels in vitro. The resolution of macrophage infiltration was reduced in both the lung and the peritoneal cavity of HIV-Tg mice. Taken together, our study described the organ-specific alteration of macrophage dynamics in HIV-Tg mice. The delayed resolution of macrophage infiltration might constitute a risk factor for the development of multiple comorbidities in PLWH.
Highlights
Combination antiretroviral therapy significantly improved the longevity of people living with HIV-1 (PLWH), improving immune function and decreasing opportunistic infections
Our study describes the organ-specific alterations in leukocytes dynamics in HIV-Tg mice
No differences were found in lung PMNC levels in wild type (WT) and HIV-Tg mice injected with PBS
Summary
Combination antiretroviral therapy (cART) significantly improved the longevity of people living with HIV-1 (PLWH), improving immune function and decreasing opportunistic infections. Chronic long-term HIV-1 infection is complicated by the increased rates of chronic medical conditions in aging population, including cardiovascular and neurological diseases, metabolic syndrome, and non-infectious respiratory disease, which summarily contribute to HIV-1 morbidity and mortality [1,2]. The mechanism of multiple comorbidities in PLWH population is rather multifactorial and includes high prevalence of risk behaviors in the HIV-infected populations, low levels of persistent viremia, chronic inflammation and persistent immune abnormalities. The gut mucosa plays an important role in the pathogenesis of HIV-1 infection. During the early acute phase of infection, about 80% of HIV-infected CD4+ T cells are located in the gut mucosa [4]. The loss of intestinal T cells results in increased gut permeability and Viruses 2020, 12, 277; doi:10.3390/v12030277 www.mdpi.com/journal/viruses
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
