CD4 T cells are rapidly depleted from tuberculosis granulomas following acute SIV co-infection

作者：Taylor W. Foreman, Christine E Nelson, Keith D. Kauffman, Nickiana E. Lora, Caian L. Vinhaes, Danielle E. Dorosky, Shunsuke Sakai, Felipe Gómez, Joel D. Fleegle, Melanie Parham, Shehan Perera, Cecilia S. Lindestam Arlehamn, Alessandro Sette, Jason M. Brenchley, Artur T. L. Queiroz, Bruno B. Andrade, Juraj Kabát, Laura E. Via, Daniel L. Barber · 发表于：Cell Reports · 年份：2022 · DOI：10.1016/j.celrep.2022.110896 · 被引用次数：40 · 研究领域：HIV Research and Treatment、Immune Cell Function and Interaction、Tuberculosis Research and Epidemiology

HIV/Mycobacterium tuberculosis (Mtb) co-infected individuals have an increased risk of tuberculosis prior to loss of peripheral CD4 T cells, raising the possibility that HIV co-infection leads to CD4 T cell depletion in lung tissue before it is evident in blood. Here, we use rhesus macaques to study the early effects of simian immunodeficiency virus (SIV) co-infection on pulmonary granulomas. Two weeks after SIV inoculation of Mtb-infected macaques, Mtb-specific CD4 T cells are dramatically depleted from granulomas, before CD4 T cell loss in blood, airways, and lymph nodes, or increases in bacterial loads or radiographic evidence of disease. Spatially, CD4 T cells are preferentially depleted from the granuloma core and cuff relative to B cell-rich regions. Moreover, live imaging of granuloma explants show that intralesional CD4 T cell motility is reduced after SIV co-infection. Thus, granuloma CD4 T cells may be decimated before many co-infected individuals experience the first symptoms of acute HIV infection.