Spatial Point Pattern Analysis Identifies Mechanisms Shaping the Skin Parasite Landscape in Leishmania donovani Infection

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Increasing evidence suggests that in hosts infected with parasites of the Leishmania donovani complex, transmission of infection to the sand fly vector is linked to parasite repositories in the host skin. However, a detailed understanding of the dispersal (the mechanism of spread) and dispersion (the observed state of spread) of these obligatory-intracellular parasites and their host phagocytes in the skin is lacking. Using endogenously fluorescent parasites as a proxy, we apply image analysis combined with spatial point pattern models borrowed from ecology to characterize dispersion of parasitized myeloid cells (including ManR+ and CD11c+ cells) and predict dispersal mechanisms in a previously described immunodeficient model of L. donovani infection. Our results suggest that after initial seeding of infection in the skin, heavily parasite-infected myeloid cells are found in patches that resemble innate granulomas. Spread of parasites from these initial patches subsequently occurs through infection of recruited myeloid cells, ultimately leading to self-propagating networks of patch clusters. This combination of imaging and ecological pattern analysis to identify mechanisms driving the skin parasite landscape offers new perspectives on myeloid cell behavior following parasitism by L. donovani and may also be applicable to elucidating the behavior of other intracellular tissue-resident pathogens and their host cells.

Original languageEnglish
Article number795554
Number of pages7
JournalFrontiers in immunology
Publication statusPublished - 16 Dec 2021

Bibliographical note

Copyright © 2021 Doehl, Ashwin, Brown, Romano, Carmichael, Pitchford and Kaye.


  • Animals
  • CD11 Antigens/metabolism
  • Cluster Analysis
  • DNA-Binding Proteins/genetics
  • Disease Models, Animal
  • Host-Parasite Interactions
  • Image Processing, Computer-Assisted
  • Insect Vectors/parasitology
  • Leishmania donovani/immunology
  • Leishmaniasis, Visceral/immunology
  • Mannose Receptor/metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Models, Theoretical
  • Myeloid Cells/immunology
  • Phlebotomus/parasitology
  • Skin/immunology
  • Spatial Analysis

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