Abstract
BackgroundInterleukin 32 (IL-32) is a pro-inflammatory cytokine induced in patients with American tegumentary leishmaniasis (ATL) caused by Leishmania braziliensis. Here, we investigated whether IL-32 is also expressed in patient lesions caused by L. amazonensis. In addition, we evaluated experimental L. amazonensis and L. braziliensis infections in C57BL/6 transgenic mice for human IL-32γ (IL-32γTg) in comparison with wild-type (WT) mice that do not express the IL-32 gene.ResultsHuman cutaneous lesions caused by L. amazonensis express higher levels of IL-32 than healthy control skin. In mice, the presence of IL-32γ promoted the control of cutaneous lesions caused by L. braziliensis, but not lesions caused by L. amazonensis in an ear dermis infection model. In addition, IL-32γTg mice displayed less tissue parasitism and inflammation in IL-32γTg than WT mice during the healing phase of L. braziliensis infection. Production of antigen-specific pro-inflammatory cytokines was higher in IL-32γTg mice than in WT mice during L. braziliensis infection but not during L. amazonensis infection.ConclusionsHuman cutaneous lesions caused by L. amazonensis express high levels of IL-32. In mice, the presence of IL-32γ contributes to the lesion healing caused by L. braziliensis but not by L. amazonensis. Data suggest that despite the ability for both species to induce IL-32 in humans, the connections between this cytokine and other immune players induced by related species of parasites can lead to distinct outcomes of the murine infections.
Highlights
Interleukin 32 (IL-32) is a pro-inflammatory cytokine induced in patients with American tegumentary leishmaniasis (ATL) caused by Leishmania braziliensis
Expression of IL-32 in lesions of patients with ATL caused by L. amazonensis We previously demonstrated that IL-32 is highly expressed in cutaneous and mucosal lesions of patients with ATL infected with Leishmania (Viannia) spp., mainly L. braziliensis
The role of IL-32 in experimental lesions caused by L. amazonensis or L. braziliensis To understand the precise role of IL-32 in ATL, we infected human IL-32γTg and WT mice with either L. amazonensis or L. braziliensis
Summary
Interleukin 32 (IL-32) is a pro-inflammatory cytokine induced in patients with American tegumentary leishmaniasis (ATL) caused by Leishmania braziliensis. American tegumentary leishmaniasis (ATL) is an infectious disease caused by Leishmania protozoan, affecting the skin, oral or nasal mucosa. Humans or mice infected with L. braziliensis present a stronger cellular immune response against the parasites than human or mice infected with L. amazonensis [5, 6]. L. braziliensis infections cause small cutaneous lesions that regress after a few weeks in C57BL/6 mice. In these mice, it has been demonstrated that the IL-12-IFN-γ/TNF-α-NO axis controls the parasite infection [7,8,9].
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