PD-1 blockade exacerbates <i>Mycobacterium tuberculosis</i> infection in rhesus macaques.

ABSTRACT: 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 proinflammator

SUBMITTER: Kauffman KD 

PROVIDER: S-EPMC8300572 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature