Roles of IFN-γ and γδ T Cells in Protective Immunity Against Blood-Stage Malaria

Abstract

Malaria is caused by infection with Plasmodium parasites. Various studies with knockout mice have indicated that IFN-γ plays essential roles in protective immunity against blood-stage Plasmodium infection. However, after Plasmodium infection, increased IFN-γ production by various types of cells is involved not only in protective immunity, but also in immunopathology. Recent reports have shown that IFN-γ acts as a pro-inflammatory cytokine to induce not only the activation of macrophages, but also the generation of uncommon myelolymphoid progenitor cells after Plasmodium infection. However, the effects of IFN-γ on hematopoietic stem cells and progenitor cells are unclear. Therefore, the regulation of hematopoiesis by IFN-γ during Plasmodium infection remains to be clarified. Although there are conflicting reports concerning the significance of γδ T cells in protective immunity against Plasmodium infection, γδ T cells may respond to infection and produce IFN-γ as innate immune cells in the early phase of blood-stage malaria. Our recent studies have shown that γδ T cells express CD40 ligand and produce IFN-γ after Plasmodium infection, resulting in the enhancement of dendritic cell activation as part of the immune response to eliminate Plasmodium parasites. These data suggest that the function of γδ T cells is similar to that of NK cells. Although several reports suggest that γδ T cells have the potential to act as memory cells for various infections, it remains to be determined whether memory γδ T cells are generated by Plasmodium infection and whether memory γδ T cells can contribute to the host defense against re-infection with Plasmodium. Here, we summarize and discuss the effects of IFN-γ and the various functions of γδ T cells in blood-stage Plasmodium infection.

Impact of Malaria Preexposure on Antiparasite Cellular and Humoral Immune Responses after Controlled Human Malaria Infection

“…NK cells are rapidly activated by malaria parasites, contribute to the early IFN-␥ response during blood-stage infection (64), and can eliminate infected erythrocytes in vivo in a contact-dependent manner (65). Importantly, there is a functional dichotomy: the rarer CD56bright cells are more prominent in lymphatic tissues and are superior cytokine producers, while the CD56dim subset harbors a stronger cytotoxic potential (66)(67)(68).…”

Osteonecrosis of the Jaw Developed in Mice

“…6). Therefore, the engrafted h-␥␦ T cells were likely to be a source of Th1 cytokines such as TNF-␣ and IFN-␥ (42).…”

Plasmodium falciparum Infection of Human Volunteers Activates Monocytes and CD16 + Dendritic Cells and Induces Upregulation of CD16 and CD1c Expression

“…The latter are activated and expanded during controlled and natural malaria infection (19,29), and schizont-stimulated pDCs are able to activate ␥␦T cells (10). The degree to which this expansion and activation of ␥␦T cells may be related to altered expression of CD1c on APCs remains to be investigated.…”

“…Although BAFF production alone cannot be used as a marker for normal APC function or activation, this adds to the hypothesis that APCs are not impaired by a malaria infection per se but might merely gain alternative functions. In addition to HLA-peptide recognition, protection against malaria is associated with ␥␦T cells expressing invariant T-cell receptors, which can be activated by lipid-presenting molecules of the CD1 family (18,19). Antigen uptake for presentation …”