Decreased IL-10 and IL-13 production and increased CD44hi T cell recruitment contribute to Leishmania major immunity induced by non-persistent parasites

Abstract

Leishmaniasis is currently classified as category 1 disease, i.e. emerging and uncontrolled. Since the importance of persistent infection for maintaining an effective long-lasting protective response is controversial, the present study asks whether immunisation with non-persistent parasites leads to protection against Leishmania infection and to the recruitment of T cells of a specific phenotype. Our study shows that vaccination of susceptible BALB/c mice with live Leishmania major phosphomannomutase-deficient parasites, which are avirulent and non-persistent in vivo, leads to protection against infection. Immunisation with phosphomannomutase-deficient parasites neither leads to differences in IFN-γ, IL-12, IL-4 production nor alters the expression of effector and memory markers, including CD62L, IL-7Rα and IL-2Rα, when compared with unvaccinated controls. Observed protection is due to the ability of vaccinated animals to suppress early IL-10 and IL-13 production and to recruit a higher number of antigen-experienced CD44^hiCD4⁺ and CD44^hiCD8⁺ T cells into draining LN following infection. Thus, expansion of T-cell numbers and their rapid recruitment to LN upon infection as well as the restriction of IL-13 and IL-10 production leading to high IFN-γ/IL-10 ratio play an important role in protection against Leishmania affecting the outcome of the disease in favour of the host.