TH1-Polarized TFH Cells Delay Naturally-Acquired Immunity to Malaria.

Xi Zen Yap,Robert W Sauerwein,Lucie S P Hustin

doi:10.3389/fimmu.2019.01096

Abstract

Humoral immunity is a critical effector arm for protection against malaria but develops only slowly after repeated infections. T cell-mediated regulatory dynamics affect the development of antibody responses to Plasmodium parasites. Here, we hypothesize that T follicular helper cell (TFH) polarization generated by repeated Plasmodium asexual blood-stage infections delays the onset of protective humoral responses. IFN-γ production promotes polarization toward TFH1 and increased generation of regulatory follicular helper cells (TFR). Delineating the mechanisms that drive TH1 polarization will provide clues for appropriate induction of lasting, protective immunity against malaria.

Highlights

Better models of TFH will be required to study these differences and assess the functional relationship between TFH subsets and the generation of humoral immunity more thoroughly: what phenotypes are generated by B-cells co-stimulated by TFH1, the quality of the antibody response, and whether their ability to differentiate into LLPCs or classical MBCs is impacted by malaria-generated TFH1s
Malaria infection, especially repeated infection with high parasitaemia, may generate “inappropriate” TH1-like T cell responses that fail to provide the adequate environment for long-lasting HI
This may be due to (i) compromised TFH help, reducing the generation of functional GC and development of typical memory B-cells, leading to a loss of HI longevity; (ii) increased proliferation of regulatory subsets such as TFR which may further inhibit HI by decreasing TFH activation and proliferation; (iii) a strong TH1-like immune signature characterized by high production of IFN-γ, illustrated by the increased fraction of TH1 and other TH1-like cells, including the TFH1 subset

Summary

Introduction

Malaria infection, especially repeated infection with high parasitaemia, may generate “inappropriate” TH1-like T cell responses that fail to provide the adequate environment for long-lasting HI. It is unclear whether the blood-derived TFH differ functionally from their GC counterparts.

Results

Conclusion