| First Author | Kauffman KD | Year | 2021 |
| Journal | Sci Immunol | Volume | 6 |
| Issue | 55 | PubMed ID | 33452107 |
| Mgi Jnum | J:331279 | Mgi Id | MGI:7386984 |
| Doi | 10.1126/sciimmunol.abf3861 | Citation | Kauffman KD, et al. (2021) PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques. Sci Immunol 6(55) |
| abstractText | Boosting immune cell function by targeting the coinhibitory receptor PD-1 may have applications in the treatment of chronic infections. Here, we examine the role of PD-1 during Mycobacterium tuberculosis (Mtb) infection of rhesus macaques. Animals treated with anti-PD-1 monoclonal antibody developed worse disease and higher granuloma bacterial loads compared with isotype control-treated monkeys. PD-1 blockade increased the number and functionality of granuloma Mtb-specific CD8 T cells. In contrast, Mtb-specific CD4 T cells in anti-PD-1-treated macaques were not increased in number or function in granulomas, expressed increased levels of CTLA-4, and exhibited reduced intralesional trafficking in live imaging studies. In granulomas of anti-PD-1-treated animals, multiple proinflammatory cytokines were elevated, and more cytokines correlated with bacterial loads, leading to the identification of a role for caspase 1 in the exacerbation of tuberculosis after PD-1 blockade. Last, increased Mtb bacterial loads after PD-1 blockade were found to associate with the composition of the intestinal microbiota before infection in individual macaques. Therefore, PD-1-mediated coinhibition is required for control of Mtb infection in macaques, perhaps because of its role in dampening detrimental inflammation and allowing for normal CD4 T cell responses. |
