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J Immunol. 2017 Jul 1;199(1):107-118. doi: 10.4049/jimmunol.1601989. Epub 2017 Jun 2.

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

Author information

1
Clinical Immunology Unit, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland.
2
University of Basel, Basel, 4001 Switzerland.
3
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
4
Department of Mathematics and Statistics, Boston University, Boston, MA 02215.
5
Department of Global Health, University of Washington, Seattle, WA 98195.
6
Center for Infectious Disease Research, Seattle, WA 98109.
7
Benaroya Research Institute, Seattle, WA 98101.
8
Ifakara Health Institute, Bagamoyo Research and Training Centre, Bagamoyo, Tanzania; and.
9
Sanaria Inc., Rockville, MD 20850.
10
Clinical Immunology Unit, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland; Claudia.Daubenberger@unibas.ch mprlic@fhcrc.org.
11
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; Claudia.Daubenberger@unibas.ch mprlic@fhcrc.org.

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-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.

PMID:
28576979
PMCID:
PMC5528886
DOI:
10.4049/jimmunol.1601989
[Indexed for MEDLINE]
Free PMC Article

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