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

• Published in: Cell reports (Cambridge) Vol. 39; no. 9; p. 110896
• Main Authors: Foreman, Taylor W., Nelson, Christine E., Kauffman, Keith D., Lora, Nickiana E., Vinhaes, Caian L., Dorosky, Danielle E., Sakai, Shunsuke, Gomez, Felipe, Fleegle, Joel D., Parham, Melanie, Perera, Shehan R., Lindestam Arlehamn, Cecilia S., Sette, Alessandro, Brenchley, Jason M., Queiroz, Artur T.L., Andrade, Bruno B., Kabat, Juraj, Via, Laura E., Barber, Daniel L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.05.2022
• Subjects: CD4 T cells; granulomas; live imaging; SIV; tuberculosis; live imaging; CP: Immunology; SIV; CD4 T cells; tuberculosis; CP: Microbiology; granulomas
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110896

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. [Display omitted] •SIV rapidly replicates in Mtb granulomas of co-infected macaques•Granuloma CD4 T cells are depleted before those in blood, BAL, LNs, or spleen•CCR5+Eomes− Mtb-specific Th1 and Th1∗ cells in granulomas are preferentially depleted•SIV co-infection reduces motility of CD4 T cells in granulomas HIV-mediated destruction of CD4 T cells enhances susceptibility to Mycobacterium tuberculosis. Using macaques, Foreman et al. show that CD4 T cells in granulomas are depleted very rapidly after SIV co-infection, indicating that loss of immunity at the site of bacterial replication occurs long before signs of peripheral T cell depletion.