T follicular helper cells regulate the activation of B lymphocytes and antibody production during Plasmodium vivax infection.

Abstract:

:Although the importance of humoral immunity to malaria has been established, factors that control antibody production are poorly understood. Follicular helper T cells (Tfh cells) are pivotal for generating high-affinity, long-lived antibody responses. While it has been proposed that expansion of antigen-specific Tfh cells, interleukin (IL) 21 production and robust germinal center formation are associated with protection against malaria in mice, whether Tfh cells are found during Plasmodium vivax (P. vivax) infection and if they play a role during disease remains unknown. Our goal was to define the role of Tfh cells during P. vivax malaria. We demonstrate that P. vivax infection triggers IL-21 production and an increase in Tfh cells (PD-1+ICOS+CXCR5+CD45RO+CD4+CD3+). As expected, FACS-sorted Tfh cells, the primary source of IL-21, induced immunoglobulin production by purified naïve B cells. Furthermore, we found that P. vivax infection alters the B cell compartment and these alterations were dependent on the number of previous infections. First exposure leads to increased proportions of activated and atypical memory B cells and decreased frequencies of classical memory B cells, whereas patients that experienced multiple episodes displayed lower proportions of atypical B cells and higher frequencies of classical memory B cells. Despite the limited sample size, but consistent with the latter finding, the data suggest that patients who had more than five infections harbored more Tfh cells and produce more specific antibodies. P. vivax infection triggers IL-21 production by Tfh that impact B cell responses in humans.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Figueiredo MM,Costa PAC,Diniz SQ,Henriques PM,Kano FS,Tada MS,Pereira DB,Soares IS,Martins-Filho OA,Jankovic D,Gazzinelli RT,Antonelli LRDV

doi

10.1371/journal.ppat.1006484

subject

Has Abstract

pub_date

2017-07-10 00:00:00

pages

e1006484

issue

7

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-17-00317

journal_volume

13

pub_type

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