Abstract
Don’t Eat Me’ signals are required for resolution of cutaneous Leishmania major infection 4368
The Journal of immunology (1950), Vol.214(Supplement_1), vkaf2832062
11/01/2025
DOI: 10.1093/jimmun/vkaf283.2062
Abstract
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)
Details
- Title: Subtitle
- Don’t Eat Me’ signals are required for resolution of cutaneous Leishmania major infection 4368
- Creators
- Hanna D. Paton - University of IowaPrajwal Gurung - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.214(Supplement_1), vkaf2832062
- DOI
- 10.1093/jimmun/vkaf283.2062
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- Oxford University Press
- Grant note
- National Institutes of Health (NIH): R01AI155425, T32AI007511 U.S. Department of Veterans Affairs (VA): I0BX006091
R01AI155425; VA I0BX006091; T32AI007511
- Alternative title
- IMMUNOLOGY2025™ Abstracts
- Language
- English
- Date published
- 11/01/2025
- Academic Unit
- Infectious Diseases; Internal Medicine
- Record Identifier
- 9985035040702771
Metrics
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