| First Author | Xu W | Year | 2021 |
| Journal | Immunity | Volume | 54 |
| Issue | 3 | Pages | 526-541.e7 |
| PubMed ID | 33515487 | Mgi Jnum | J:337591 |
| Mgi Id | MGI:6706523 | Doi | 10.1016/j.immuni.2021.01.003 |
| Citation | Xu W, et al. (2021) Early innate and adaptive immune perturbations determine long-term severity of chronic virus and Mycobacterium tuberculosis coinfection. Immunity 54(3):526-541.e7 |
| abstractText | Chronic viral infections increase severity of Mycobacterium tuberculosis (Mtb) coinfection. Here, we examined how chronic viral infections alter the pulmonary microenvironment to foster coinfection and worsen disease severity. We developed a coordinated system of chronic virus and Mtb infection that induced central clinical manifestations of coinfection, including increased Mtb burden, extra-pulmonary dissemination, and heightened mortality. These disease states were not due to chronic virus-induced immunosuppression or exhaustion; rather, increased amounts of the cytokine TNFalpha initially arrested pulmonary Mtb growth, impeding dendritic cell mediated antigen transportation to the lymph node and subverting immune-surveillance, allowing bacterial sanctuary. The cryptic Mtb replication delayed CD4 T cell priming, redirecting T helper (Th) 1 toward Th17 differentiation and increasing pulmonary neutrophilia, which diminished long-term survival. Temporally restoring CD4 T cell induction overcame these diverse disease sequelae to enhance Mtb control. Thus, Mtb co-opts TNFalpha from the chronic inflammatory environment to subvert immune-surveillance, avert early immune function, and foster long-term coinfection. |
