Dataset Information

Controlled Human Malaria Infection Leads to Long-Lasting Changes in Innate and Innate-like Lymphocyte Populations.

ABSTRACT: Animal model studies highlight the role of innate-like lymphocyte populations in the early inflammatory response and subsequent parasite control following Plasmodium infection. IFN-? production by these lymphocytes likely plays a key role in the early control of the parasite and disease severity. Analyzing human innate-like T cell and NK cell responses following infection with Plasmodium has been challenging because the early stages of infection are clinically silent. To overcome this limitation, we examined blood samples from a controlled human malaria infection (CHMI) study in a Tanzanian cohort, in which volunteers underwent CHMI with a low or high dose of Plasmodium falciparum sporozoites. The CHMI differentially affected NK, NKT (invariant NKT), and mucosal-associated invariant T cell populations in a dose-dependent manner, resulting in an altered composition of this innate-like lymphocyte compartment. Although these innate-like responses are typically thought of as short-lived, we found that changes persisted for months after the infection was cleared, leading to significantly increased frequencies of mucosal-associated invariant T cells 6 mo postinfection. We used single-cell RNA sequencing and TCR ??-chain usage analysis to define potential mechanisms for this expansion. These single-cell data suggest that this increase was mediated by homeostatic expansion-like mechanisms. Together, these data demonstrate that CHMI leads to previously unappreciated long-lasting alterations in the human innate-like lymphocyte compartment. We discuss the consequences of these changes for recurrent parasite infection and infection-associated pathologies and highlight the importance of considering host immunity and infection history for vaccine design.

SUBMITTER: Mpina M

PROVIDER: S-EPMC5528886 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Controlled Human Malaria Infection Leads to Long-Lasting Changes in Innate and Innate-like Lymphocyte Populations.

Mpina Maxmillian M Maurice Nicholas J NJ Yajima Masanao M Slichter Chloe K CK Miller Hannah W HW Dutta Mukta M McElrath M Juliana MJ Stuart Kenneth D KD De Rosa Stephen C SC McNevin John P JP Linsley Peter S PS Abdulla Salim S Tanner Marcel M Hoffman Stephen L SL Gottardo Raphael R Daubenberger Claudia A CA Prlic Martin M

Journal of immunology (Baltimore, Md. : 1950) 20170602 1

Animal model studies highlight the role of innate-like lymphocyte populations in the early inflammatory response and subsequent parasite control following <i>Plasmodium</i> infection. IFN-γ production by these lymphocytes likely plays a key role in the early control of the parasite and disease severity. Analyzing human innate-like T cell and NK cell responses following infection with <i>Plasmodium</i> has been challenging because the early stages of infection are clinically silent. To overcome t ...[more]

PMID: 28576979

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Dataset Information

Controlled Human Malaria Infection Leads to Long-Lasting Changes in Innate and Innate-like Lymphocyte Populations.

Publications

Controlled Human Malaria Infection Leads to Long-Lasting Changes in Innate and Innate-like Lymphocyte Populations.

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