IL-1 signalling is dispensable for protective immunity in Leishmania-resistant mice

Abstract

Leishmaniasis is a parasitic disease affecting 12 million people. Control of infection (e.g. in C57BL ⁄ 6 mice) results from IL-12-dependent production of IFNc by Th1 ⁄ Tc1 cells. In contrast, BALB ⁄ c mice succumb to infection because of preferential Th2-type cytokine induction. Infected dendritic cells (DC) represent important sources of IL-12. Genetically determined differences in DC IL-1a ⁄ b production contribute to disease outcome. Whereas the course of disease was not dramatically altered in IL-1RI ) ⁄ ) mice, local administration of IL-1a to infected C57BL ⁄ 6 mice improved disease outcome. To definitively elucidate the involvement of IL-1 in immunity against leishmaniasis, we now utilized IL-1a ⁄ b-double-deficient C57BL ⁄ 6 mice. C57BL ⁄ 6 mice are believed to be a good surrogate model for human, self limited cutaneous leishmaniasis (CL). Leishmania major-infected IL-1a ⁄ b ) ⁄ ) mice were resistant to experimental CL comparable to controls. In addition, DC-based vaccination against leishmaniasis in C57BL ⁄ 6 mice was independent of IL-1. Thus, in Leishmania-resistant C57BL ⁄ 6 mice, IL-1 signalling is dispensable for protection.

Induction, Propagation, and Activity of Host Nitric Oxide: Lessons from Leishmania Infection

“…Interleukin-1//b C57BL/6 mice deficient for IL-1//b or IL-1RI (the receptor for IL-1/ and IL-1b) can perfectly control L. major infection, and in some cases even exhibit a less severe pathology and lower parasite burden than WT mice [35,36]. This suggests that IL-1/ or IL-b signaling is dispensable for the control of Leishmania parasites in resistant mice.…”

“…However, the defect in iNOS induction observed in this case may result from a defect in IFNg production. In fact, since IL-1 signaling deeply alters T cell development and effector functions during L. major infection [36], it is particularly difficult to isolate the respective role of these cytokines from that of IFNg. A recent study highlighted the close interaction between IL-1 and IFNg signaling during L. major infection by demonstrating that in this context, skin commensals promote IFNg secretion by effector T cells through IL-1 signaling [39].…”

Old World cutaneous leishmaniasis: diagnosis and treatment

“…65 In an experimental study realized in mice, Leishmania major-infected IL-1α/β(-/-) mice were resistant to experimental CL compared to controls. 66 A recent trial carried by Haruko Ota et al showed that pretreatment of macrophages with the combination of IFN-γ and IL-12 induces resistance to L. major at the early phase of the infection. 67 Immune prophylaxis…”

Assessment of β-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in L. major infected BALB/c mice

“…Whereas it contributed to NO-mediated resistance to L. amazonensis, L. braziliensis and L. infantum-chagasi [45], IL-1 production was irrelevant [46] or detrimental in early L. major infections and the effect should be mediated by Th2-bias adaptive immune response [47]. IL-1b was one of the genes significantly stronger up-regulated in resistant C57BL/6 mice vs susceptible BALB/c mice although the analysis was made from 16 h L. major infected mice [48].…”