| First Author | Minkah NK | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 3950 |
| PubMed ID | 31477704 | Mgi Jnum | J:279299 |
| Mgi Id | MGI:6362189 | Doi | 10.1038/s41467-019-11819-0 |
| Citation | Minkah NK, et al. (2019) Innate immunity limits protective adaptive immune responses against pre-erythrocytic malaria parasites. Nat Commun 10(1):3950 |
| abstractText | Immunization with attenuated whole Plasmodium sporozoites constitutes a promising vaccination strategy. Compared to replication-deficient parasites, immunization with replication-competent parasites confers better protection and also induces a type I IFN (IFN-1) response, but whether this IFN-1 response has beneficial or adverse effects on vaccine-induced adaptive immunity is not known. Here, we show that IFN-1 signaling-deficient mice immunized with replication-competent sporozoites exhibit superior protection against infection. This correlates with superior CD8 T cell memory including reduced expression of the exhaustion markers PD-1 and LAG-3 on these cells and increased numbers of memory CD8 T cells in the liver. Moreover, the adoptive transfer of memory CD8 T cells from the livers of previously immunized IFN-1 signaling-deficient mice confers greater protection against liver stage parasites. However, the detrimental role of IFN-1 signaling is not CD8 T cell intrinsic. Together, our data demonstrate that liver stage-engendered IFN-1 signaling impairs hepatic CD8 T cell memory via a CD8 T cell-extrinsic mechanism. |
