Controlled human malaria infection leads to long-lasting changes in innate and innate-like lymphocyte populations

Mpina, Maxmillian and Maurice, Nicholas J. and Yajima, Masanao and Slichter, Chloe K. and Miller, Hannah W. and Dutta, Mukta and McElrath, M. Juliana and Stuart, Kenneth D. and De Rosa, Stephen C. and McNevin, John P. and Linsley, Peter S. and Abdulla, Salim and Tanner, Marcel and Hoffman, Stephen L. and Gottardo, Raphael and Daubenberger, Claudia A. and Prlic, Martin. (2017) Controlled human malaria infection leads to long-lasting changes in innate and innate-like lymphocyte populations. Journal of immunology (Baltimore, Md. : 1950), 199. pp. 107-118.

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Official URL: http://edoc.unibas.ch/55637/

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Animal model studies highlight the role of innate-like lymphocyte populations in the early inflammatory response and subsequent parasite control following Plasmodium 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 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 αβ-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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Health Interventions > Malaria Interventions (Lengeler)
UniBasel Contributors:Daubenberger, Claudia and Tanner, Marcel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:The American Association of Immunologists, Inc.
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:03 Oct 2017 08:23
Deposited On:03 Oct 2017 08:23

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