학술논문
Lymph-node resident [CD8a.sup.+] dendritic cells capture antigens from migratory malaria sporozoites and induce [CD8.sup.+] T cell responses
RESEARCH ARTICLE
RESEARCH ARTICLE
Document Type
Report
Author
Source
PLoS Pathogens. February 2015, Vol. 11 Issue 2
Subject
Language
English
ISSN
1553-7366
Abstract
Introduction Sterile immunity against live sporozoite challenge is elicited by immunization with radiation-attenuated sporozoites [1] and is, in part, mediated by [CD8.sup.+] T cells specific for the Plasmodium circumsporozoite (CS) [...]
Malaria infection begins when a female Anopheles mosquito injects Plasmodium sporozoites into the skin of its host during blood feeding. Skin-deposited sporozoites may enter the bloodstream and infect the liver, reside and develop in the skin, or migrate to the draining lymph nodes (DLNs). Importantly, the DLN is where protective [CD8.sup.+] T cell responses against malaria liver stages are induced after a dermal route of infection. However, the significance of parasites in the skin and DLN to [CD8.sup.+] T cell activation is largely unknown. In this study, we used genetically modified parasites, as well as antibody-mediated immobilization of sporozoites, to determine that active sporozoite migration to the DLNs is required for robust [CD8.sup.+] T cell responses. Through dynamic in vivo and static imaging, we show the direct uptake of parasites by lymph-node resident DCs followed by [CD8.sup.+] T cell-DC cluster formation, a surrogate for antigen presentation, in the DLNs. A few hours after sporozoite arrival to the DLNs, [CD8.sup.+] T cells are primed by resident [CD8[alpha].sup.+] DCs with no apparent role for skin-derived DCs. Together, these results establish a critical role for lymph node resident [CD8[alpha].sup.+] DCs in [CD8.sup.+] T cell priming to sporozoite antigens while emphasizing a requirement for motile sporozoites in the induction of [CD8.sup.+] T cell-mediated immunity.
Malaria infection begins when a female Anopheles mosquito injects Plasmodium sporozoites into the skin of its host during blood feeding. Skin-deposited sporozoites may enter the bloodstream and infect the liver, reside and develop in the skin, or migrate to the draining lymph nodes (DLNs). Importantly, the DLN is where protective [CD8.sup.+] T cell responses against malaria liver stages are induced after a dermal route of infection. However, the significance of parasites in the skin and DLN to [CD8.sup.+] T cell activation is largely unknown. In this study, we used genetically modified parasites, as well as antibody-mediated immobilization of sporozoites, to determine that active sporozoite migration to the DLNs is required for robust [CD8.sup.+] T cell responses. Through dynamic in vivo and static imaging, we show the direct uptake of parasites by lymph-node resident DCs followed by [CD8.sup.+] T cell-DC cluster formation, a surrogate for antigen presentation, in the DLNs. A few hours after sporozoite arrival to the DLNs, [CD8.sup.+] T cells are primed by resident [CD8[alpha].sup.+] DCs with no apparent role for skin-derived DCs. Together, these results establish a critical role for lymph node resident [CD8[alpha].sup.+] DCs in [CD8.sup.+] T cell priming to sporozoite antigens while emphasizing a requirement for motile sporozoites in the induction of [CD8.sup.+] T cell-mediated immunity.