Role of Treg, Breg and other cytokine sets in host protection and immunopathology during human leishmaniasis: Are they potential valuable markers in clinical settings and vaccine evaluation?

Leishmaniasis is a vector-borne disease caused by obligate intracellular protozoan parasites that can infect humans and other mammals. Pro- and anti-inflammatory cytokines are important regulators of innate and specific responses in Leishmania infection. Resistance to leishmaniasis is related to T helper 1 (Th1) response with the production of pro-inflammatory cytokines: IL-12, IL-1β, IFN-γ, TNF-α, IL-2 leading to activation of macrophages and parasite killing. Instead, a more intense Th2 (IL-4, IL-5, IL-13), Treg (IL-10 and TGF-β) and Breg response (IL-10 and IL-35) are related to parasite persistence through the inhibition of macrophage activation, which promotes the escape from host immune system. Interestingly, a cytokine involved in the parasite killing in one form of leishmaniasis may be "pathogen friendly" in another form of the disease. To date, few studies are focusing on the role of Treg and Breg cytokines in human models of leishmaniasis; therefore, further investigations are needed to clarify their potential role in the diagnosis and prognosis of such protozoan infections, as well as in the development of vaccines against leishmaniasis. This review summarizes the current knowledge about the role of cytokines produced by Th1, Th2, Treg, and Breg cells involved in Leishmania disease progression and host protection. Some cytokines might play a role as diagnostic and prognostic clinical markers, or they could represent a novel approach leading to new anti-leishmaniasis therapies. Overall, advances in knowledge of the complex network of cytokines secreted by immune cells could help to better understand signaling pathways and host immune responses during Leishmania infection. This approach would allow these mediators to be used as therapeutic strategies against leishmaniasis.