Informace o publikaci
Behind the curtain of the protective effect against leishmaniasis: A new role for eosinophils?
| Autoři | |
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| Rok publikování | 2025 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | The protective effect against leishmaniasis is a known phenomenon, as the pathology of cutaneous leishmaniasis, demonstrated in mice and caused by Leishmania major, is significantly milder if the mice are repeatedly exposed to the blood feeding of non-infectious Phlebotomus sand flies prior to infection. It is generally believed that this protection results from immunization with salivary antigens, which induce a specific cellular immune response characterized by the so-called delayed-type hypersensitivity (DTH) reaction. During DTH, activated proinflammatory macrophages infiltrate the sand fly feeding site, with a characteristic peak at 48 hours after feeding. These activated macrophages produce nitric oxide (NO), a potent leishmanicidal molecule, thereby reducing the parasite load. However, previous studies assessed this effect only in mice infected at least 7 days after the last exposure to sand fly saliva, not during the peak of the DTH reaction (at day 2 after the last exposure). To fill this gap, we immunized mice twice at weekly intervals and infected them either two (D2) or seven (D7) days after the last immunization. Paradoxically, L. major lesions were larger in mice infected at D2, at the peak of expected protective DTH reaction. In the follow-up study presented here, we focused on the immune response of mice at time points D2 and D7, emphasizing the myeloid leukocyte populations in the ear—macrophages, neutrophils, and eosinophils. Mice underwent three immunization feedings at weekly intervals and were sacrificed either at D2 or D7 postlast feeding. In line with the above-described paradigm, we demonstrated that leukocytes migrated to the feeding site at D2 in response to the induced delayed-type hypersensitivity (DTH) reaction. Interestingly, using a combination of cytometric and histological approaches, we found that among the three examined cell populations, eosinophils were by far the most abundant. As expected, macrophages, the typical Leishmania host cells, were also present in the infiltrate, but surprisingly, they were not polarized proinflammatory as expected in Leishmania-protected mice. Neutrophils known for their role in propagating infection, were only rarely present compared to other cell populations. At D7, infiltrated myeloid cells were overall less abundant, but cell population patterns remained consistent. The dominant presence of eosinophils, coupled with the lack of proinflammatory macrophages, suggests a previously unrecognized role for eosinophils in the protective effect against Leishmania. Further experiments investigating this issue are underway in our laboratory. |