Plasmodium vivax infection alters the peripheral immunoregulatory network of 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 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 . 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 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.