Plasmodium vivax infection changes the peripheral immunoregulatory network: CD4 T follicular cells and B cells

Regulatory and effector cell responses to Plasmodium vivax, the most common human malaria parasite outside Africa, remain understudied in naturally infected populations. Here, we describe peripheral CD4(+) T- and B-cell populations during and shortly after an uncomplicated P. vivax infection in 38 continuously exposed adult Amazonians. Consistent with previous observations, we found an increased frequency in CD4(+)CD45RA(-)CD25(+)FoxP3(+) T regulatory cells that express the inhibitory molecule CTLA-4 during the acute infection, with a sustained expansion of CD21(-)CD27(-) atypical memory cells within the CD19(+) B-cell compartment. Both Th1- and Th2-type subsets of CXCR5(+)ICOS(hi)PD-1(+) circulating T follicular helper (cTfh) cells, which are thought to contribute to antibody production, were induced during P. vivax infection, with a positive correlation between overall cTfh cell frequency and IgG antibody titers to the P. vivax blood-stage antigen MSP1(19). We identified significant changes in cell populations that had not been described in human malaria, such as an increased frequency of CTLA-4(+) T follicular regulatory cells that antagonize Tfh cells, and a decreased frequency of circulating CD24(hi)CD27(+) B regulatory cells in response to acute infection. In conclusion, we disclose a complex immunoregulatory network that is critical to understand how naturally acquired immunity develops in P. vivax malaria.

Automated summary

Regulatory and effector cell responses to Plasmodium vivax infection were studied in a group of 38 Amazonian adults. The study found increased frequency of CD4(+)CD45RA(-)CD25(+)FoxP3(+) T regulatory cells and expanded population of CD21(-)CD27(-) atypical memory cells within the CD19(+) B-cell compartment during acute infection. The study also identified changes in cell populations that had not been described in human malaria, such as increased frequency of CTLA-4(+) T follicular regulatory cells and decreased frequency of circulating CD24(hi)CD27(+) B regulatory cells. These findings contribute to the understanding of naturally acquired immunity in P. vivax malaria.