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

Author(s)

Ferreira, Natalia S. ; Lima, Nathalia F. ; Sulczewski, Fernando B. ; Soares, Irene S. ; Ferreira, Marcelo U. ; Boscardin, Silvia B.

• Document type: Journal article
• Source: European Journal of Immunology; v. N/A, p. 15-pg., 2023-05-24.

Abstract

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. (AU)

• FAPESP's process: 18/07142-9 - Influence of STAT1, STAT3, STAT5 and STAT6 Signaling Pathways on Conventional Dendritic Cells in the Instruction of the T-Cell Auxiliary Response
• Grantee: Silvia Beatriz Boscardin
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/18740-9 - Scientific bases for residual malaria elimination in the Brazilian Amazon
• Grantee: Marcelo Urbano Ferreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/50108-0 - Sero-surveillance tools for targeting Plasmodium vivax infections and monitoring malaria control and elimination efforts in Amazonian countries
• Grantee: Irene da Silva Soares
• Support Opportunities: Regular Research Grants