Regulatory T cells
Few data are available about regulatory T cells (Treg) during T. cruzi acute infection (most studies address the role of Treg in the pathology of chronic cardiopathy, which is not the topic of this chapter). CD4+CD25+ Tregs expressing PD-1 or CTLA-4 have been detected during acute T. cruzi infection.142,143 The amastigote protein SSP4 is involved in the induction of TGF-в-producing Treg,144 as well as a galectine-1-dependent mechanism.145 Tregs favor parasite growth by limiting IFN-y production. However, their immunosuppressive activity may be rather beneficial by restraining inflammation, thereby prolonging survival.143
The recently disclosed role of IL-17 in T. cruzi infection
Since its discovery in 1993, IL-17 represented the hallmark of the Th17 cell subset, having an important role in protecting the host against extracellular pathogens (particularly fungi) by activating neutrophils. It has more recently been documented that other T cell subsets such as y&T and natural killer T (NKT) cells, as well a subset of ILCs, can also produce IL-17 in response to innate stimuli.32,146
Interest in IL-17 in T. cruzi infection has followed the demonstration, in 2010, of the crucial beneficial involvement of IL-17 in the control of acute infection.147,148 It was shown that IL-17 was mainly produced by CD41 T cells during the acute infection, though CD81 T cells58 and NKT and y&T cells149 also contribute. Of note, the ability to induce IL-17 production may vary according to the parasite strain/DTU.58
A still more fascinating discovery is that B cells have been recently disclosed as a major early source of IL-17 in T. cruzi infection through an unprecedented way, independent of Ag recognition by BCR or of TLR engagement.150 The authors showed that parasite TS modifies the glycosylation pattern of surface CD45
molecule of B cells, leading to IL-17 release by a noncanonical signaling mechanism. This constitutes one of the rare examples described to date that B cells bring more than antibodies to the fight against pathogens.151
Maximal IL-17 levels are reached during the acute phase of T. cruzi infection. IL-17 is thought to reduce inflammation and mortality by recruiting suppressive IL-10-producing neutrophils.152 The mechanism by which IL-17 limits parasite multiplication is less clear. It might rely to restriction of IFN-Y-related control mechanisms (Th17 cells may inhibit Th1 response148). It has however recently been shown that IL-17 is able to limit parasite multiplication in macrophages through a particular mechanism: though favoring the entry of parasites into macrophages, IL-17 facilitates their killing by prolonging their residency in endosomal/lysosomal compartments, which enhances exposure to antimicrobial effectors.153 This mechanism may be strongly strain-dependent.