Antiretroviral therapy (ART) has altered the clinical environment of HIV, shifting the traditional focus on AIDS-induced opportunistic infections and cancers to one in which the most common morbidities and causes of death differ little from those seen in noninfected adults. The primary distinction is that these conditions, which include cardiovascular diseases, declining physical function, neurocognitive and neuropsychiatric disorders, and alterations in body composition, first manifest in people living with HIV (PLWH) approximately 5–10 years earlier than HIV-uninfected individuals.1–3 The accelerated aging in HIV has now been further complicated by the emergence of SARS-CoV-2 infection and postacute COVID syndrome (PACS). Exploring the linkages—and points of difference—between these 2 viral conditions, while promoting multidisciplinary collaboration among researchers to identify new perspectives on HIV and aging, was the aim of “HIV and Aging in the Era of ART and COVID-19 inter-CFAR symposium.”
In addition to their well characterized role in allergic inflammation, recent data confirm that mast cells play a more extensive role in a variety of immune responses. However, their contribution to autoimmune and neurologic disease processes has not been investigated. Experimental allergic encephalomyelitis (EAE) and its human disease counterpart, multiple sclerosis, are considered to be CD4+ T cell-mediated autoimmune diseases affecting the central nervous system. Several lines of indirect evidence suggest that mast cells could also play a role in the pathogenesis of both the human and murine disease. Using a myelin oligodendrocyte glycoprotein (MOG)-induced model of acute EAE, we show that mast cell-deficient W/W(v) mice exhibit significantly reduced disease incidence, delayed disease onset, and decreased mean clinical scores when compared with their wild-type congenic littermates. No differences were observed in MOG-specific T and B cell responses between the two groups, indicating that a global T or B cell defect is not present in W/W(v) animals. Reconstitution of the mast cell population in W/W(v) mice restores induction of early and severe disease to wild-type levels, suggesting that mast cells are critical for the full manifestation of disease. These data provide a new mechanism for immune destruction in EAE and indicate that mast cells play a broader role in neurologic inflammation.