Opsonized antigen activates Vδ2+ T cells via CD16/FCγRIIIa in individuals with chronic malaria exposure.

Autor: Farrington LA; Department of Medicine, University of California San Francisco, San Francisco, California, United States of America., Callaway PC; Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.; Infectious Disease and Immunity Graduate Group, University of California Berkeley, California, United States of America., Vance HM; Department of Medicine, University of California San Francisco, San Francisco, California, United States of America., Baskevitch K; Department of Medicine, University of California San Francisco, San Francisco, California, United States of America., Lutz E; Department of Medicine, University of California San Francisco, San Francisco, California, United States of America., Warrier L; Department of Medicine, University of California San Francisco, San Francisco, California, United States of America., McIntyre TI; Department of Medicine, University of California San Francisco, San Francisco, California, United States of America., Budker R; Department of Medicine, University of California San Francisco, San Francisco, California, United States of America., Jagannathan P; Department of Medicine, Stanford University, Stanford, California, United States of America., Nankya F; Infectious Diseases Research Collaboration, Kampala, Uganda., Musinguzi K; Infectious Diseases Research Collaboration, Kampala, Uganda., Nalubega M; Infectious Diseases Research Collaboration, Kampala, Uganda., Sikyomu E; Infectious Diseases Research Collaboration, Kampala, Uganda., Naluwu K; Infectious Diseases Research Collaboration, Kampala, Uganda., Arinaitwe E; Infectious Diseases Research Collaboration, Kampala, Uganda., Dorsey G; Department of Medicine, University of California San Francisco, San Francisco, California, United States of America., Kamya MR; Infectious Diseases Research Collaboration, Kampala, Uganda.; College of Health Sciences, Makerere University, Kampala, Uganda., Feeney ME; Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.; Department of Pediatrics, University of California San Francisco, San Francisco, California, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2020 Oct 21; Vol. 16 (10), pp. e1008997. Date of Electronic Publication: 2020 Oct 21 (Print Publication: 2020).
DOI: 10.1371/journal.ppat.1008997
Abstrakt: Vγ9Vδ2 T cells rapidly respond to phosphoantigens produced by Plasmodium falciparum in an innate-like manner, without prior antigen exposure or processing. Vδ2 T cells have been shown to inhibit parasite replication in vitro and are associated with protection from P. falciparum parasitemia in vivo. Although a marked expansion of Vδ2 T cells is seen after acute malaria infection in naïve individuals, repeated malaria causes Vδ2 T cells to decline both in frequency and in malaria-responsiveness, and to exhibit numerous transcriptional and phenotypic changes, including upregulation of the Fc receptor CD16. Here we investigate the functional role of CD16 on Vδ2 T cells in the immune response to malaria. We show that CD16+ Vδ2 T cells possess more cytolytic potential than their CD16- counterparts, and bear many of the hallmarks of mature NK cells, including KIR expression. Furthermore, we demonstrate that Vδ2 T cells from heavily malaria-exposed individuals are able to respond to opsonized P.falciparum-infected red blood cells through CD16, representing a second, distinct pathway by which Vδ2 T cells may contribute to anti-parasite effector functions. This response was independent of TCR engagement, as demonstrated by blockade of the phosphoantigen presenting molecule Butyrophilin 3A1. Together these results indicate that Vδ2 T cells in heavily malaria-exposed individuals retain the capacity for antimalarial effector function, and demonstrate their activation by opsonized parasite antigen. This represents a new role both for Vδ2 T cells and for opsonizing antibodies in parasite clearance, emphasizing cooperation between the cellular and humoral arms of the immune system.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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