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Review
. 2020 Jan;293(1):88-114.
doi: 10.1111/imr.12835.

Using two phases of the CD4 T cell response to blood-stage murine malaria to understand regulation of systemic immunity and placental pathology in Plasmodium falciparum infection

Komi Gbedande  1 , Victor H Carpio  2 , Robin Stephens  1   2
Affiliations
Review

Using two phases of the CD4 T cell response to blood-stage murine malaria to understand regulation of systemic immunity and placental pathology in Plasmodium falciparum infection

Komi Gbedande et al. Immunol Rev. 2020 Jan.

Abstract

Plasmodium falciparum infection and malaria remain a risk for millions of children and pregnant women. Here, we seek to integrate knowledge of mouse and human T helper cell (Th) responses to blood-stage Plasmodium infection to understand their contribution to protection and pathology. Although there is no complete Th subset differentiation, the adaptive response occurs in two phases in non-lethal rodent Plasmodium infection, coordinated by Th cells. In short, cellular immune responses limit the peak of parasitemia during the first phase; in the second phase, humoral immunity from T cell-dependent germinal centers is critical for complete clearance of rapidly changing parasite. A strong IFN-γ response kills parasite, but an excess of TNF compared with regulatory cytokines (IL-10, TGF-β) can cause immunopathology. This common pathway for pathology is associated with anemia, cerebral malaria, and placental malaria. These two phases can be used to both understand how the host responds to rapidly growing parasite and how it attempts to control immunopathology and variation. This dual nature of T cell immunity to Plasmodium is discussed, with particular reference to the protective nature of the continuous generation of effector T cells, and the unique contribution of effector memory T cells.

Keywords: Plasmodium; CD4 T cells; T follicular; cytokines.

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Conflict of interest statement

Conflict of Interest Statement: The authors have no conflicts of interest related to this manuscript

Figures

Figure 1.
Figure 1.
Two phase adaptive immune response to Plasmodium spp.. Alignment of parasitemia of A) P. chabaudi chabaudi (AS) with B) P. yoelii (17XNL) and C) kinetics of T cell phenotypes in mice each week of infection. Th1-like response peaks preceeding strong germinal center response, which does not coincide with increase in GC-Tfh cells. Based on data from
Figure 2.
Figure 2.
Several transcription factors regulate T-bet in Plasmodium-induced hybrid Th1/Tfh cells. Each marker and cytokine is regulated by a unique set of overlapping signals. Based on data from
See this image and copyright information in PMC

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