’Don’t Eat Me’ signals are required for resolution of cutaneous Leishmania major infection 4368
Year: 2025
Type: article
Abstract: Description Leishmania major is a protozoan parasite causative of the disfiguring disease cutaneous leishmaniasis (CL). Current treatments, including pentavalent antimonials, are losing efficacy due to growing parasite resistance. Along with cost and access barriers, there is a critical need for more treatments. Macrophages (MΦ) are the primary reservoir of parasite in vivo. In addition to receptor mediated uptake, MΦ become infected by engulfing free parasite or infected cells/cellular debris. Parasite killing or survival within infected MΦ is governed by M1/M2 polarization. We hypothesized that disrupting phagocytosis checkpoints such as CD47-SIRPα, the “don’t eat me” signal, would impact disease severity. Mounting evidence points to a critical role for CD47 during viral and bacterial infection, while parasitic infection remains largely uninvestigated. Thus, we subcutaneously infected footpads of Cd47-/-, wildtype, and littermate control mice on a resistant C57BL/6 background. Cd47-/- mice were highly susceptible compared to controls, shown by increase in lesion frequency, swelling, and parasite load. Infecting Sirpα-/- mice revealed similar disease severity to Cd47-/-, indicating that CD47-SIRPα is vital for healing. Next, we performed cellular analysis on footpad skin ∼80 days post infection. CD45+ cellularity was increased in Cd47-/-, and myeloid markers like CD11c, CD11b, MHCII, and F4/80 had altered expression. This indicates that CD47 can influence myeloid cell effector function. Funding Sources R01AI155425; VA I0BX006091; T32AI007511 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)
Source: The Journal of Immunology
Authors: Hanna D. Paton, Prajwal Gurung
Institution: University of Iowa
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416446854
FWCI:
Cites:
Cited by:
Related to: