Unknown

Dataset Information

0

Innate immunity limits protective adaptive immune responses against pre-erythrocytic malaria parasites.


ABSTRACT: 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.

SUBMITTER: Minkah NK 

PROVIDER: S-EPMC6718385 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Innate immunity limits protective adaptive immune responses against pre-erythrocytic malaria parasites.

Minkah Nana K NK   Wilder Brandon K BK   Sheikh Amina A AA   Martinson Thomas T   Wegmair Lisa L   Vaughan Ashley M AM   Kappe Stefan H I SHI  

Nature communications 20190902 1


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 sup  ...[more]

Similar Datasets

| S-EPMC9803926 | biostudies-literature
| S-EPMC5476299 | biostudies-literature
| S-EPMC8155606 | biostudies-literature
| S-EPMC5853061 | biostudies-literature
| S-EPMC3569641 | biostudies-literature
| S-EPMC3184181 | biostudies-literature
| S-EPMC5544665 | biostudies-literature
| S-EPMC4674243 | biostudies-literature
| S-EPMC6060232 | biostudies-literature
| S-EPMC8438027 | biostudies-literature